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  • pharmacokinetics  (29)
  • Chromatographie, Gas  (9)
  • Immunocytochemistry
  • Springer  (42)
  • Periodicals Archive Online (PAO)
  • 1975-1979  (42)
  • 1975  (42)
Collection
Keywords
Publisher
  • Springer  (42)
  • Periodicals Archive Online (PAO)
Years
  • 1975-1979  (42)
Year
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 97-105 
    Details
    ISSN: 1432-1041
    Keywords: Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561557
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  • 2
    Electronic Resource
    Electronic Resource
    Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 157-160 
    Details
    ISSN: 1432-1041
    Keywords: Isosorbide dinitrate ; pharmacokinetics ; metabolism ; pharmacological action ; nitrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An oral dose of 5 mg of14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral dose. Up to 99% of an oral dose of isosorbide dinitrate was excreted during 5 days, mainly in the urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567108
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics — Uses and abuses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 241-248 
    Details
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is apparent from studying recent articles on pharmacokinetics that a number of misunder-standings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567122
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and side-effects of clonazepam and its 7- amino-metabolite in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 249-254 
    Details
    ISSN: 1432-1041
    Keywords: Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567123
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  • 5
    Electronic Resource
    Electronic Resource
    Anticoagulant effect and plasma kinetics of fluorophenindione after a single dose in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 271-275 
    Details
    ISSN: 1432-1041
    Keywords: Fluorophenindione ; vitamin K antagonist ; pharmacokinetics ; loading dose ; anticoagulant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After administration of a single loading dose (80 mg p.o.) of fluorophenindione, the prothrombin level decreased to 37 % in 24 h, and the effect lasted for 48 h. Accordingly, fluorophenindione can be classified as an anticoagulant with an “intermediate” effect. Its elimination half-life was 31 h, which is longer than that of phenindione, because of the greater stability of the fluorinated derivate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567127
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  • 6
    Electronic Resource
    Electronic Resource
    Kinetics of nortriptyline in man according to a two compartment model (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562660
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  • 7
    Electronic Resource
    Electronic Resource
    Disposition of placentally transferred carbamazepine (Tegretol®) in the newborn (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 283-284 
    Details
    ISSN: 1432-1041
    Keywords: Newborn infants ; carbamazepine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma elimination of carbamazepine (Tegretol®) was studied in five newborns who had got the drug transplacentally from their epileptic mothers. The half-lives ranged from 8.2 – 27.7 hours which is comparable or even shorter than those found in adults after a single oral dose, but in the same range as those found in adults after multiple oral doses. This suggests that the newborns' drug metabolizing capacity has been induced during fetal life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567129
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  • 8
    Electronic Resource
    Electronic Resource
    The serum level approach to individualization of drug dosage (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 1-8 
    Details
    ISSN: 1432-1041
    Keywords: Serum concentrations ; individual drug dosage ; pharmacokinetics ; individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The importance of individualizing the dosage of potent drugs in order to maximize their therapeutic effectiveness and safety is generally accepted. Whenever possible the dosage of a drug should be “titrated” directly in each patient against the intensity of its therapeutic or toxic actions. Unfortunately, for many drugs convenient clinical yardsticks of the intensity of their pharmacologic effects are lacking. Determination of the serum concentration of such compounds can help to guide adjustment of dosage during their therapeutic use. By measuring the serum level of drugs one bypasses the largest source of individual differences in doseeffect relationships — the pharmacokinetic variation between subjects. However, the relationship between the serum concentration of a drug and the intensity of its pharmacodynamic action is influenced by many other factors, which must always be considered in interpretation of serum levels. Therapeutic decisions should never be based solely on the serum concentration of a compound, nor can such measurements ever substitute for careful medical observation and judgement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613423
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  • 9
    Electronic Resource
    Electronic Resource
    On the fate of furosemide in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 57-61 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; gastrointestinal absorption ; diuretics ; glucuronides ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 35S-furosemide was administered orally (n=7) or i.v. (n=2) to healthy subjects. The average gastrointestinal uptake estimated by comparison of the urinary recovery of label and the areas under the plasma curves after the two routes of administration was 65%. The half life of radioactivity in the plasma after oral35S-furosemide was 90 ± 17 min (estimated on the slope between 2 and 6 h); the corresponding figure after35S-furosemide i.v. was 47–53 min (slope 0.5–4 h). There was probably a slower phase after 4–6 h. Fractionation of labelled material in urine from two subjects demonstrated that approximately two thirds of the label recovered at 24 h had the same chromatographic properties as furosemide. A major part of the metabolite(s) was probably furosemide glucuronide. There was no evidence that 4-chloro-5-sulfamoylanthranilic acid was formed in man. The total urinary recovery of label (5–7 d) after oral and intravenous administration was 55.1±3.2 (mean±SD) and 82–84%, respectively. After35S-furosemide i.v., 6–9% of the label was recovered in faeces, and it could not be accounted for solely by biliary excretion of furosemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613429
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  • 10
    Electronic Resource
    Electronic Resource
    Serum concentrations of ampicillin and probenecid and ampicillin excretion after repeated oral administration of a pivampicillin-probenecid salt (MK-356) (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 125-129 
    Details
    ISSN: 1432-1041
    Keywords: Pivampicillin ; ampicillin ; probenecid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty male volunteers received oral doses (2100, 1050, and 525 mg) of a pivampicillin-probenecid salt in a 1 to 1 molar ratio (MK-356) at 12 hour intervals. After each dose peak serum concentrations of probenecid were observed 2 hours later than peak concentrations of ampicillin. Following the first dose of MK-356 the apparent elimination rate of ampicillin was dose-dependent and did not follow first order kinetics, as it showed a longer apparent half life after a higher dose. An equal dose of MK-356 administered 12 hours later caused an increase in the peak serum ampicillin level greater than expected from the concentration of ampicillin after the preceding dose. In twelve male volunteers who received at random 525 mg of MK-356 or 350 mg of pivampicillin, each three times daily for 4 days, the areas under the ampicillin concentration curve were the same after the first or last dose of either drug. When 2100 or 1050 mg of MK-356 was taken as an initial dose, 30 to 40 per cent of the ampicillin was recovered from urine in the ensuing 12 hours. The results indicate that when at least 400 mg probenecid was coadministered twice daily with 700 mg pivampicillin (MK-356), the peak serum concentrations of ampicillin were increased and its elimination rate slowed following successive doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614008
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  • 11
    Electronic Resource
    Electronic Resource
    Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan®) in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 135-145 
    Details
    ISSN: 1432-1041
    Keywords: Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614010
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 155-159 
    Details
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614012
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  • 13
    Electronic Resource
    Electronic Resource
    The physiological disposition of etilefrine in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 179-187 
    Details
    ISSN: 1432-1041
    Keywords: Etilefrine ; pharmacokinetics ; metabolism ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and metabolic studies with3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, β) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with the hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614015
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  • 14
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration to man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 169-178 
    Details
    ISSN: 1432-1041
    Keywords: Heptabarbital ; heptabarbital sodium ; pharmacokinetics ; plasma concentration ; single and multiple dose kinetics ; relative bioavailability ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 – 5.0 µg/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets was quite slow and peak level times varied from 1.5 to 4 h. The sodium salt was absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 – 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 – 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin® tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614014
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  • 15
    Electronic Resource
    Electronic Resource
    Interaction of indomethacin and acetylsalicylic acid as shown by the serum concentrations of indomethacin and salicylate (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 199-207 
    Details
    ISSN: 1432-1041
    Keywords: Indomethacin ; acetylsalicylic acid ; drug interaction ; oral and rectal dosing ; serum levels ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A clinical-pharmacological study was performed to determine the effect of acetylsalicylic acid upon the serum concentration of indomethacin. 14 rheumatic patients were given indomethacin orally (25 mg × 4 for 4 days) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily), and 21 rheumatic patients were given indomethacin rectally in the morning (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily). On comparison with treatment with oral or rectal indomethacin alone, it was found that peak serum concentrations of indomethacin were significantly reduced (1% level), the times of the peaks were not shifted, and the areas beneath the serum concentration curves of indomethacin were smaller, but significantly so only if compared with rectal administration. In 12 rheumatic patients given indomethacin by rectum in the evening (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g (0.9 g × 3 and 1.0 g × 1 daily), the serum level of indomethacin on the following morning (after 11 h) did not differ from that found after rectal treatment. A statistically but not biologically significant difference was observed between the mean serum half-lives of indomethacin given orally and rectally. For unknown reasons, concurrent doses of acetylsalicylic acid and indomethacin made the mean serum half-life of indomethacin longer than after its oral administration, but shorter than when the same dose of indomethacin was given rectally. There was no difference between serum levels of salicylate after oral administration of acetylsalicylic acid alone or after a concurrent oral or rectal dose of indomethacin. The results have been related to those reported previously, with respect to the interaction between indomethacin and acetylsalicylic acid, the serum levels of indomethacin after oral and rectal dosing, and the serum half-life of indomethacin based upon a one- or two-compartment model. The clinical relevance of the study is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614018
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  • 16
    Electronic Resource
    Electronic Resource
    Disposition of quercetin in man after single oral and intravenous doses (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 229-234 
    Details
    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614022
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  • 17
    Electronic Resource
    Electronic Resource
    Comparison of the pharmacokinetics of glipizide and glibenclamide in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 63-69 
    Details
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; sulfonylurea ; glipizide ; glibenclamide ; pharmacokinetics ; excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Four subjects received 5 mg14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00616416
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  • 18
    Electronic Resource
    Electronic Resource
    Distribution and elimination kinetics of carbamazepine in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561556
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  • 19
    Electronic Resource
    Electronic Resource
    The dosage of Co-trimoxazole in childhood (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 217-222 
    Details
    ISSN: 1432-1041
    Keywords: Co-trimoxazole ; sulphamethoxazole ; trimethoprim ; pharmacokinetics ; paediatric-prescribing ; dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-trimoxazole, a mixture of one part trimethoprim (TMP) and five parts of sulphamethoxazole (SMX) in fixed ratio was given to 48 children aged between one and 48 months twice daily for up to seven days. Twenty were relatively healthy and 28 were very ill. Dosage was based on age. Plasma concentrations of both drugs were measured just before a dose was due and some three hours later. They were in the effective but not toxic range and serve to justify the simple regimen which generated them.
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    URL: http://dx.doi.org/10.1007/BF00567118
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    Pharmacokinetics of 5,6-trans-25-hydroxycholecalciferol, a synthetic analogue of vitamin D3, in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 255-260 
    Details
    ISSN: 1432-1041
    Keywords: Vitamin D ; renal osteodystrophy ; 5,6-trans-25-hydroxycholecalciferol ; rickets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Vitamin D analogues of high biological activity are probably useful in the treatment of renal osteodystrophy. The pharmacokinetics of the synthetic compound 5,6-trans-25-hydroxycholecalciferol have been studied in healthy subjects who were of normal vitamin D status. In comparison to natural 25-hydroxy-cholecalciferol, serum levels of the analogue were lower and its half-life in blood after oral or intravenous administration was considerably shorter. In normal subjects no increase of dihydroxylated metabolites in serum was observed within seven days of an intravenous dose.
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    URL: http://dx.doi.org/10.1007/BF00567124
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  • 21
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    Pharmacokinetics of chlormethiazole in humans (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 353-357 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
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    URL: http://dx.doi.org/10.1007/BF00562662
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  • 22
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    On the pharmacokinetics of phenacetin in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 261-265 
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    ISSN: 1432-1041
    Keywords: Phenacetin ; pharmacokinetics ; liver-first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic characteristics of the analgesic phenacetin have been determined in six healthy adults. After rapid i.v. injection of 250 mg phenacetin, the log plasma concentrations versus time curves were evaluated according to the rules of a two-compartment open model. The elimination half-life (t 1/2) β varied from 37 to 74 minutes. The volume of distribution (Vd) β ranged from 1.0 to 2.1 1 per kg body weight. The total clearance of the drug was high and approximated the average value of hepatic blood flow in normal adults. In agreement with this finding, the bioavailability of a small oral dose of phenacetin (0.25 g) was almost nil, as the bulk of the drug was cleared during its first pass through the liver. With large oral doses (1.0 g) the first-pass effect decreased and availability increased. The results are discussed and related to current general views of the liver-first-pass phenomenon.
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    URL: http://dx.doi.org/10.1007/BF00567125
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  • 23
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    Plasma kinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 337-341 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; carbamamazepine-10,11-epoxide ; pharmacokinetics ; induction of metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (Tegretol®) was administered orally to four patients as a single dose, and one week later three times daily for 15–21 days. The plasma half-lives of the drug were shorter in all patients after multiple doses (20.9±5.0 hours) than after the initial single dose (35.6±15.3 hours). During multiple doses the plasma concentrations of the metabolite carbamazepine-10,11-epoxide followed those of the parent drug. The steady-state plasma concentrations expected during multiple doses were calculated from the pharmacokinetic parameters obtained in the single dose studies. The calculated levels were higher (17.2±7.2 µg/ml) than the observed maximal concentrations (8.4±1.6 µg/ml on day 4), which were obtained 3–4 days after starting the multiple doses. The levels tended to decrease further during the experimental period. The results suggest that carbamazepine induces its own metabolism in man.
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    URL: http://dx.doi.org/10.1007/BF00562659
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  • 24
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    Growth hormone-release inhibiting hormone (GH-RIH) pathway of the rat hypothalamus revealed by the unlabeled antibody peroxidase-antiperoxidase method (1975)
    Springer
    Cell & tissue research 160 (1975), S. 423-430 
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    ISSN: 1432-0878
    Keywords: Growth hormone-release inhibiting hormone ; Somatostatin ; Hypothalamus ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Utilizing the unlabeled antibody enzyme method, we investigated the distribution of hypothalamic elements immunoreactive with antibodies to growth hormonerelease inhibiting hormone (GH-RIH). Immunostained elements, resembling neural processes, are distributed along a pathway corresponding to a portion of the tuberoinfundibular tract. However, GH-RIH fibers are caudal, dorsal and medial to LH-RH fibers detected by the same technique. Similar topographic arrangements are noted in coronal and sagittal sections. Comparable results were obtained with two different preparations of antisera to GH-RIH. No cell bodies specifically stained by anti-GH-RIH were detected. Our data agree with those of other investigators using immunohistochemical techniques.
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    URL: http://dx.doi.org/10.1007/BF00225761
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  • 25
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    Ultrastructural immunocytochemical localization of neurophysin and vasopressin in the median eminence and posterior pituitary of the guinea pig (1975)
    Springer
    Cell & tissue research 159 (1975), S. 291-301 
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    ISSN: 1432-0878
    Keywords: Neurophysin ; Vasopressin ; Median eminence ; Electron microscopy ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary With the use of tissue prepared by freeze-substitution and the unlabelled antibody enzyme technique, neurophysin and vasopressin were localized at the ultrastructural level in the posterior pituitary and median eminence of the guinea pig. In the posterior pituitary neurophysin was found in the large neurosecretory granules (1300–1500 Å) of axons, Herring bodies, and nerve terminals. In some of these axons immunoreactive neurophysin was found outside of granules in the axoplasm. By light microscopy neurophysin was found in both the zona interna and zona externa of the median eminence; this was confirmed by electron microscopy. In the zona interna as in the posterior pituitary, neurophysin was localized both inside and outside the large neurosecretory granules. In the zona externa, immunoreactive deposit was primarily located in granules with a diameter of 900–1100 Å in nerve terminals abutting on the primary portal plexus. The distribution of vasopressin paralleled that of neurophysin except that the hormone was rarely extragranular. These results demonstrate for the first time that both neurophysin and vasopressin are present in granules of axons that are in contact with the hypophysial portal vasculature.
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    URL: http://dx.doi.org/10.1007/BF00221777
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  • 26
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    Ontogeny of the pig hypothalamic neurosecretory system with particular reference to the distribution of neurophysin (1975)
    Springer
    Cell & tissue research 164 (1975), S. 543-557 
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    ISSN: 1432-0878
    Keywords: Magnocellular hypothalamic nuclei ; Fetal and neonatal pigs ; Anti-porcine neurophysin serum ; Immunocytochemistry ; Slab gradient polyacrylamide gel electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The immunoperoxidase cytochemical reaction was applied to the localization of neurophysin-containing elements in the fetal and adult pig hypothalamus. In the 60 day fetal pig, cells of the supraoptic nucleus (SON) were the only structures in the hypothalamus in which neurophysin was detected. However, by 87 days the cell bodies in both the SON and paraventricular nucleus (PVN) contained neurophysin-like material. The distribution of immunoreactive material in the 111 day fetal animal was similar to that found in the adult pig. In transverse section of the mature pig the SON exists in two discrete components; an antero-lateral group of cells connected by scattered cells to a smaller postero-medial group. Anteriorly, the PVN appears as a line of cells bordering the third ventricle but as we proceed posteriorly the dorsal aspect expands laterally to give a wedge-shaped group of cells. In mid-sagittal sections, the cells of the PVN are distributed over a wide area of the anterior hypothalamus in a triangular profile. The borders between the SON and PVN became more difficult to define in medial sections than in lateral sections. Continuous gradient polyacrylamide gel electrophoresis was carried out on the neural lobe extracts from fetal, newborn and adult pigs. Proteins with an electrophoretic mobility similar to that of porcine neurophysins-I,-II and -III were present in the newborn and 98 day fetal pig. It is concluded that material immunoreactive with anti-neurophysin serum is present in the hypothalamus of the 60 day fetal pig. Furthermore, at late fetal development and during the postnatal period it is tentatively suggested that the neurophysin present in the pituitaries of these animals is chemically identical with that of adult neurophysin.
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    URL: http://dx.doi.org/10.1007/BF00219944
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  • 27
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    Immunocytochemical analysis of cells in the pars tuberalis of the rat hypophysis with antisera to hormones of the pars distalis (1975)
    Springer
    Cell & tissue research 156 (1975), S. 443-449 
    Details
    ISSN: 1432-0878
    Keywords: Pituitary gland ; Cytology ; Pars tuberalis ; Immunocytochemistry ; Luteinizing hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The objective was to acquire evidence regarding the secretory capacity of cells in the pars tuberalis of the rat pituitary by the application of immunocytochemical staining. For this purpose the conjugated antibody and immunoglobulin-enzyme bridge techniques were utilized with antisera to the following hormones of the pars distalis: human somatotropin, human thyrotropin, human β-melanotropin, ovine luteinizing hormone (LH), porcine β17–39-corticotropin, and β1–24-corticotropin. Only LH-containing cells were demonstrated. They were exceedingly rare in the cephalic pars tuberalis beneath the median eminence. The frequency of LH-cells was greater in the pars tuberalis associated with the infundibulum and increased distally. LH-cells were most common ventrolateral to the infundibular stem and occurred singly and in clusters. These results indicate that following hypophysectomy the portion of the pars tuberalis that remains in situ has the capacity to secrete only LH of all the pars distalis hormones.
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  • 28
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    Pantolacton aus Coenzym A. Bestimmung von Pantothensäure (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 277 (1975), S. 124-124 
    Details
    ISSN: 1618-2650
    Keywords: Pantothensäure, Pantolacton ; Chromatographie, Gas ; Hydrolyse von Coenzym A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00602082
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  • 29
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    Ermittlung des Vernetzungsgrades und Beladungszustandes von Ionenaustauschern auf Kunstharzbasis durch Pyrolyse-Gas-Chromatographie (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 277 (1975), S. 9-17 
    Details
    ISSN: 1618-2650
    Keywords: Ermittlung des Vernetzungsgrades, Beladungszustandes von Ionenaustauschern ; Chromatographie, Gas ; Pyrolyse, Kunstharzbasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Zur besseren Reproduzierbarkeit der Zusammensetzung des Pyrolysates bei der Pyrolyse-Gas-Chromatographie wird eine spezielle Eingabenanordnung mit Trägergasumschaltung beschrieben und deren Einfluß auf die Bildung der Pyrolyseprodukte und auf die Retentionszeiten mit einer Modellsubstanz untersucht. Mit Hilfe der Trägergasumschaltung kann man die Bandenflächenverhältnisse zur Bestimmung des Vernetzungsgrades von Ionenaustauschern auf Styrol-DVB-Basis wesentlich genauer ermitteln. Da bei der Pyrolyse von Anionenaustauschern wenigerα-MSt auftritt als bei den Kationenaustauschern, sind die Bandenflächenverhältnisse bei ersteren wesentlich größer. Bei den Anionenaustauschern werden sie mit steigendem Vernetzungsgrad kleiner, wohingegen bei den Kationenaustauschern die Werte steigen. Bei 400° C erfolgt der thermische Angriff im wesentlichen an der aktiven Gruppe der Anionenaustauscher mit Styrol-DVB-Matrix. Die aus dem Gegenion entstehenden Methylester bzw. deren Zersetzungsprodukte sind charakteristische Pyrolyseprodukte. Kennzeichnend für Dowex 1 ist das Auftreten von Trimethylamin, für Dowex 2 das von Acetaldehyd. Somit ist es mit der Pyrolyse-Gas-Chromatographie möglich, zusätzlich zur Matrix, Art und Struktur der funktionellen Gruppe sowie Substitutionsstelle der Ankergruppen an der Matrix auch Vernetzungsgrad und Beladungszustand von Ionenaustauschern zu ermitteln.
    Notes: Abstract A special introduction device with switching of carrier gas for improving the reproducibility of pyrolysate composition in pyrolysis gas-chromatography has been described. Its influence on the formation of pyrolysis products and on retention times has been studied on a model substance. The peak area ratios for determining the degree of cross-linking in ion exchangers on styrene-DVB basis can be estimated considerably more accurately with the help of carrier gas switching. Since anion exchangers yield lessα-methylstyrene on pyrolysis than do cation exchangers, their peak area ratios are appreciably larger. Increasing the degree of cross-linking lowers the ratios with the anion exchangers and raises them with the cation exchangers. At 400° C the thermal attack on anion exchangers with styrene-DVB matrix occurs mainly at the active group. The methyl esters or their decomposition products formed from the counter ions are characteristic pyrolysis products. A feature of Dowex 1 is the formation of trimethylamine; of Dowex 2, acetaldehyde. In this way, pyrolysis gas-chromatography enables information about the degree of cross linking and the nature of the anion of ion exchangers, as well as about the matrix, type and structure of the functional group and position of substitution of the anchor group in the matrix to be obtained.
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    Ultrapolare Mischphasen zur GLC-Bestimmung von Benzol (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 277 (1975), S. 31-32 
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    ISSN: 1618-2650
    Keywords: Best. von Benzol ; Chromatographie, Gas ; ultrapolare Mischphasen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00591874
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    Derivation of general equations for linear mammillary models when the drug is administered by different routes (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 203-218 
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    ISSN: 1573-8744
    Keywords: pharmacokinetics ; general equations ; mammillary models ; route of drug administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A general disposition equation for a linear mammillary model consisting of ncompartments is derived. This equation is used to derive disposition equations for the central compartment when drug input occurs into the central compartment and when drug input occurs into a peripheral compartment. The derivation of equations that describe the entire time course of drug in a particular compartment after intravenous, intramuscular, oral, and rectal drug administration is also presented.
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  • 32
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    Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 181-192 
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    ISSN: 1573-8744
    Keywords: digoxin ; two-compartment model ; pharmacokinetics ; urinary excretion ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Normal subjects were given 0.75 mg of intravenous digoxin as a bolus and a 1-hr infusion, Radio-immunoassayed serum concentrations obtained over 48 hr and urinary excretion rates over 6 days were simultaneously fitted to a two- compartment open model by computer nonlinear least-squares regression. Serum concentration data alone were also fitted by this program. There was good agreement in calculated parameters between the two routes of administration in five of eight subjects, but the infusion mode of administration produced less variability in the apparent pharmacokinetic constants. The β half-life values obtained from serum concentration data alone (24.2 hr) underestimated the half-lives obtained by the simultaneous fit (44.1 hr). The steady-state volume of distribution of digoxin averaged 590±164 liters (±1 sd).The renal clearance of digoxin (140±41 ml/min/1.73 m 2 )was significantly higher than creatinine clearance (101±13 ml/min/ 1.73 m 2 ),indicating tubular secretion of the drug. Digoxin body clearances were 188±44 ml/min/ 1.73 m 2 ,indicating elimination of 25% of the dose by nonrenal mechanisms. Urinary excretion data are essential for proper pharmacokinetic analysis of digoxin disposition and reveal a slower rate of elimination than that suggested by earlier studies which determined only serum concentrations.
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    Pharmacokinetics in man of theN-acetylated metabolite of proeainamide (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 223-235 
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    ISSN: 1573-8744
    Keywords: N-acetylprocainamide ; procainamide ; pharmacokinetics ; drug metabolism ; clinical pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of N-acetylprocainamide (NAPA) have been studied in three normal subjects who received 500 mg of this compound by timed intravenous injection. Plasma N APA concentrations and urine excretion were measured by quadrupole mass fragmentography, and a three- compartment pharmacokinetic model was used for data analysis. NAPA elimination half-life and total distribution volume averaged 6.0 hr and 1.38 liters/kg, respectively. Renal excretion of unchanged NAPA accounted for 81% of its elimination, and the mean renal NAPA clearance was 179 ml/min. Approximately 2% of the injected NAPA was deacetylated to procainamide. The fate was not determined of 17% of the NAPA that was estimated to have been eliminated during the 16- hr study period.
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    Gas chromatographic determination and pharmacokinetics of 4-hydroxybutyrate in dog and mouse (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 99-113 
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    ISSN: 1573-8744
    Keywords: sodium 4-hydroxybutyrate ; pharmacokinetics ; general anesthetics ; capacity-limited elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A rapid and reproducible method was developed to extract 4-hydroxybutyrate from plasma as 4-butyrolactone for subsequent gas chromatographic (GLC) assay. The drug, an intravenous anesthetic and oral hypnotic in man, was infused into four dogs and the plasma concentration was determined by 14 C-isotope dilution and GLC. Pharmacokinetic parameters for distribution and elimination were calculated. A capacity-limited process appears to be involved in the elimination of 4-hydroxybutyrate in the dog. Macroautoradiography revealed the distribution pattern in normal and pregnant adult mice.
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    Pharmacokinetics of morphine in plasma and discrete areas of the rat brain (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 293-302 
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    ISSN: 1573-8744
    Keywords: morphine ; pharmacokinetics ; pharmacokinetic models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract After intravenous administration of an analgesic dose of morphine into rat, the time course of morphine concentrations was followed in plasma, whole brain, and four discrete areas of the brain during 8 hr. These concentration curves indicated a three-exponential function which could be described by a mammillary system of three compartments. Maximal brain levels were obtained 15–20 min after injection, showing a fairly even distribution pattern of morphine. The plasma to whole brain ratio showed three-exponential characteristics, approaching a constant value of about 4.7–4.8 after 4 hr. By use of the SAAM-25 program, the experimental data from plasma and brain were simultaneously fitted to five separate sets of three-compartment models. Results obtained implied the uniqueness of the computed transfer constants of the three-compartment model.
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    URL: http://dx.doi.org/10.1007/BF01082303
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    Pharmacokinetics in the aged: A review (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 387-418 
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    ISSN: 1573-8744
    Keywords: review ; pharmacokinetics ; elderly ; clinical considerations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Age-related differences in drug response have recently received increased attention in the medical literature. This report reviews those recent publications dealing with the study of pharmacokinetics in the aged population. The rate and extent of drug absorption do not appear to be altered to any appreciable degree in the elderly patient. However, drug disposition in the aged subject may be affected by a number of factors including alterations in protein binding, apparent volumes of distribution, and renal and/or extrarenal clearance of the drug.
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    URL: http://dx.doi.org/10.1007/BF01059473
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    Zur Analytik von Organozinnstabilisatoren (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 273 (1975), S. 19-23 
    Details
    ISSN: 1618-2650
    Keywords: Analyse von Organozinnverbindungen, Alkylzinnverbindungen, Organozinnstabilisatoren ; Chromatographie, Gas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Die quantitative Bestimmung von Mono-, Di-, Tri- und Tetraalkylzinnverbindungen in Mischungen durch Gas-Chromatographie ist möglich nach Alkylierung zu gemischten Tetraalkylzinnderivaten. Die Alkylierung mit Methyl-, Butyl- und Octylmagnesylchlorid in Diäthyläther ist quantitativ und verläuft ohne Veränderung der ursprünglichen Zinnverteilung. Sie läßt sich nicht nur auf Alkylzinnoxide und -chloride, sondern auch direkt auf Alkylzinn-thioglykolate anwenden. Die aus der Umsetzung der Thioglykolsäureester resultierenden Nebenprodukte werden von der gas-chromatographischen Analyse an Kieselgel absorbiert und die Tetraalkylzinnverbindungen mit n-Pentan eluiert. Die gas-chromatographische Trennung wird wahlweise an Carbowax oder Polyglycol 20000 durchgeführt bei Temperaturen zwischen 100 und 230° C. Die Peak-Flächen entsprechen den Gew.-% Tetraalkylzinn.
    Notes: Abstract The quantitative determination of mono-, di-, tri- and tetraalkyl tin compounds in mixture by GLC is possible after alkylation to mixed tetraalkyl tins. The alkylation with methyl-, butyl- and octyl magnesium chloride runs quantitatively without any change in the original alkyl groups attached to the tin. The method can be applied not only for alkyl tin oxides and chlorides but also directly for alkyl tin thioglycolates. The by-products resulting from the thioglycolic acid ester cleavage are absorbed on silica gel prior to GLC and the tetraalkyl tins are eluted with n-pentane. Gas-chromatographic analysis is carried out alternatively with carbowax and polyglycol 20000 at temperatures between 100 and 230° C. The peak areas correspond to the weight percentage of tetraalkyl tin.
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    Gas-chromatographische Überwachung des Extraktionsmittels bei der Wiederaufarbeitung von HTR-Brennelementen (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 273 (1975), S. 113-116 
    Details
    ISSN: 1618-2650
    Keywords: Best. von Monobutylphosphat, Dibutylphosphat in Tributylphosphat, n-Alkanen ; Chromatographie, Gas ; Überwachung der Wiederaufarbeitung von HTR-Brennelementen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Bei der Wiederaufarbeitung von HTR-Brennelementen durch Solventextraktion nach dem THOREX-Prozeß wird das als Extraktionsmittel verwendete Tributylphosphat/n-Alkan-Gemisch einer intensiven hydrolytischen und radiolytischen Beanspruchung ausgesetzt. Hauptprodukte sind Di- und Monobutylphosphat, die schon in geringen Konzentrationen durch Bildung nicht rückextrahierbarer Urankomplexe und Überführung gewisser Spaltprodukte in die wäßrige Produktphase zu Störungen bei der Extraktion führen. Beide Ester werden durch Sodawäsche aus dem bestrahlten Extraktionsmittel entfernt, welches danach wiederverwendet werden kann. Zur Kontrolle der Wirksamkeit dieser Solventwäsche, der Zusammensetzung des frischen und der Gesamtqualität des recyclierten Extraktionsmittels soll die Gas-Chromatographie innerhalb des JUPITER-Prozesses eingesetzt werden. Sie erlaubt eine quantitative Bestimmung von DBP und MBP bis zu Gehalten von etwa 25 ppm. Die Analysendauer beträgt ca. 100 min.
    Notes: Abstract During reprocessing of HTR fuel elements by the THOREX solvent extraction process the tributylphosphate/n-alcane mixture used as extractant is subject to an intensive radiolytic and hydrolytic burden. Main degradation products are di- and monobutylphosphate which in quite low concentrations disturb the solvent extraction by retention of uranium and transfer of some fission products into the aqueous product solution. Both esters are removed from the irradiated solvent by washing with a sodium carbonate solution, after which the solvent may be recycled. For a control of the efficiency of this solvent recovery procedure as well as of the composition of the fresh and recycled solvent in the JUPITER reprocessing facility, gas chromatography will be used. This method allows the determination of di- and monobutylphosphate down to concentration levels of about 25 parts per million. An analysis requires about 100 min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426269
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  • 39
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    Gas chromatography of chlorides and bromides of III-, IV- and V-group elements in the periodic table (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 274 (1975), S. 353-357 
    Details
    ISSN: 1618-2650
    Keywords: Analyse von Chloriden, Bromiden ; Chromatographie, Gas ; Elemente der III. -V. Gruppe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary The theory for the relation between retention volume and boiling point in gas chromatography was applied to the retention volumes for bromides of IV- and chlorides and bromides of III- and V-group elements in the periodic table, as an extension of the previous paper on chlorides of IV-group elements. The apparent solubility parameter of solventβδ S was separated into the non-regularity parameterβ and the solubility parameter of solventδ S, and the meaning ofβ and the value ofδ S were estimated empirically. Followingδ S values were obtained: Silicon oil DC 550 (8.1), Apiezon grease L (9.1), PEG 1500 (11.6), FeCl3 · 6 H2O (12.5), Low melting point alloy (12.5) and Ga metal (13.4).
    Notes: Zusammenfassung Die Theorie über die Beziehung zwischen Retentionsvolumen und Siedepunkt in der Gas-Chromatographie wurde auf die Retentionsvolumina der Bromide der IV. sowie der Chloride und Bromide der III. und V. Gruppe angewendet (in Fortführung der früheren Arbeit über die Chloride der IV. Gruppe). Der scheinbare Löslichkeitsparameter des Lösungsmittels (βδ S) wurde aufgetrennt in den Unregelmäßigkeitsparameter (β) und den Löslichkeitsparameter des Lösungsmittels (δ S). Die Bedeutung vonβ und der Wert vonδ S wurden empirisch bestimmt. Die folgendenδ S-Werte wurden erhalten: Siliconöl DC 550 (8,1), Apiezonfett L (9,1), PEG 1500 (11,6), FeCl3 · 6 H2O (12,5), niedrigschmelzende Legierung (12,5), Ga-Metall (13,4).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00626033
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  • 40
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    Gas-chromatographische Bestimmung von monosubstituierten Acetylenen in der C4-Fraktion (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 275 (1975), S. 27-27 
    Details
    ISSN: 1618-2650
    Keywords: Best. von Acetylen, Methylacetylen, Äthylacetylen, Vinylacetylen ; Chromatographie, Gas ; Isolierung als Acetylide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432994
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  • 41
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    Notiz über eine gas-chromatographische Bestimmung von Essigsäure und Propionsäure in Polyamid 6 (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 276 (1975), S. 127-128 
    Details
    ISSN: 1618-2650
    Keywords: Best. von Essigsäure und Propionsäure in Polyamid 6 ; Chromatographie, Gas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01165816
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  • 42
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    3-Hydroxyglutarsäuredinitril als Trennflüssigkeit für die GLC (1975)
    Springer
    Fresenius' Zeitschrift für analytische Chemie 277 (1975), S. 373-373 
    Details
    ISSN: 1618-2650
    Keywords: Verw. von 3-Hydroxyglutarsäuredinitril als Trennflüssigkeit ; Chromatographie, Gas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00423783
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