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  • Life and Medical Sciences  (479)
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  • pharmacokinetics  (115)
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  • Springer  (115)
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  • 1
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Schlagwort(e): zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 2
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 279-285 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlordiazepoxide ; alcoholic liver disease ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r=0.73, P〈0.0005) and was independent of the presence of alcoholic hepatitis. The metabolic clearance of chlordiazepoxide was significantly lower in the patients than in the normal subjects (7.6 compared to 13.8 ml/kg-h, P〈0.005). Linear regression analysis revealed a significant correlation between clearance and albumin (r=0.77, P〈0.00005). However, the predictive value of this relationship was shown to be minimal. Multiple regression analysis produced only a slight improvement in the correlation when both albumin and lactate dehydrogenase were used as variables (r=0.83, P〈0.00005). In six of the patients, a second clearance study was conducted three weeks following their initial one. All repeat subjects showed improvement both clinically and as reflected by their laboratory tests for liver injury, but there was not a significant change in their clearance of chlordiazepoxide. Multiple regression analysis of the clearance data on the initial and repeat subjects showed a significant correlation between clearance and the variables age, albumin, and lactate dehydrogenase (r=0.91, P〈0.0025). This relationship suggests that over a short period of time (where age can be considered constant) changes in albumin and lactate dehydrogenase could be potentially useful in predicting clearance changes in a single individual.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562805
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  • 3
    Digitale Medien
    Digitale Medien
    Prazosin, pharmacokinetics and concentration effect (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 177-181 
    Details
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; alpha receptor blockade ; blood pressure ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and effects of prazosin have been studied after intravenous and oral dosing (1 mg) to 6 normal male volunteers. The mean terminal (β) half-life was 2.9 h after intravenous and oral routes. Oral bioavailability was 56.9%. The effects of prazosin on blood pressure were more pronounced after intravenous than oral administration, and the hypotensive effect greater on erect blood pressure. There was a significant correlation (P〈0.02) between the fall in blood pressure and the plasma drug concentration after intravenous prazosin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562058
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  • 4
    Digitale Medien
    Digitale Medien
    The influence of duration of intravenous infusion of an acute dose on plasma concentrations of cimetidine (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 29-34 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; intravenous infusion ; pharmacokinetics ; peptic ulcer ; duration of infusion ; acute dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The use of cimetidine administered by bolus intravenous injection to critically ill patients has been associated with serious cardiac arrhythmias, due presumably to high initial plasma concentrations. The aim of this study was to determine the range of infusion times of a single 200 mg dose of cimetidine which would avoid high initial drug concentrations while maintaining a duration of effective concentrations no less than that resulting from bolus injection. Computer simulations of both maximum plasma cimetidine concentrations and duration of effective plasma cimetidine concentrations versus duration of infusion were based on mean pharmacokinetic date from 6 peptic ulcer patients who had received cimetidine 200 mg i.v. over 5 min. The simulations indicated that to reduce maximum plasma cimetidine concentrations by at least 50%, while maintaining the duration of effective plasma concentrations, the infusion time should be at least 30 min and no longer than 4.5 h. The validity of the simulations was subsequently tested in 4 of the patients, who received cimetidine 200 mg i.v. over 30 min. The mean maximum plasma concentration for the 30 min infusion (4.57±0.53 µg/ml) was, as predicted, approximately half that corresponding to bolus administration in these patients (8.97±1.96 µg/ml). Moreover, the duration of effective concentrations for the infusion (1.43±0.28 h) was significantly greater than that for the 5 min infusion (1.21±0.31 h). We suggest that where an acute intravenous dose of cimetidine (200 mg) is indicated, it should be administered over at least 30 min rather than as a bolus.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544010
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  • 5
    Digitale Medien
    Digitale Medien
    Perturbation of the switch-on of transcriptase activity in intermediate subviral particles from reovirus (1982)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 112 (1982), S. 10-18 
    Details
    ISSN: 0021-9541
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Notizen: Intermediate subviral particles (ISVP) derived from reovirus represent a simple model system for the switch-on of transcriptase function. In such particles the endogenous transcriptase is present in a switched-off form, one step removed from the switched-on state. Switch-on of transcriptase function is an active process in this system and can be triggered by K+ ions. A variety of agents which affect gene expression in cells were tested for an effect on switch-on in ISVP. Marked effects on switch-on in ISVP were observed with a diverse group of test agents, including DMSO and other solvents, BUdR, TdR, caffeine, theophylline, and temperature. The correlation in response between ISVP and cells suggests that the ISVP system may be useful as a model for studying the biochemical mechanisms underlying the perturbative effects of such agents on gene expression in cells.
    Zusätzliches Material: 14 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/jcp.1041120104
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  • 6
    Digitale Medien
    Digitale Medien
    Inhibition of the metabolism of ram spermatozoa by derivatives of α-chlorohydrin (1981)
    New York, NY : Wiley-Blackwell
    Gamete Research 4 (1981), S. 203-217 
    Details
    ISSN: 0148-7280
    Schlagwort(e): α-chlorohydrin ; antifertility agent ; ram ; sperm metabolism ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: The effects of the male antifertility agent, α-chlorohydrin, six of its derivatives, and glycidol were studied on the metabolism of washed ram spermatozoa in vitro with fructose as substrate. The α-chlorohydrin derivatives were the amino, the phosphorylated, and four glycol-bridge (ketal) compounds. All compounds except glycidol, in a concentration between 0.1 and 100 mM, reduced the aerobic glycolsis and/or oxidation of fructose. However, there was not a high correlation between the ability of these compounds to inhibit the metabolism of ram spermatozoa in vitro and their antifertility activity when administered to male rats. Other factors are clearly involved in their antifertility activity, eg, the concentration of the compounds in the epididymis and their conversion of either more or less spermicidal compounds in the body.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/mrd.1120040305
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  • 7
    Digitale Medien
    Digitale Medien
    Morphological and ultrastructural characterization of mammalian spermatozoa processed for flow cytometric DNA analyses (1984)
    New York, NY : Wiley-Blackwell
    Gamete Research 10 (1984), S. 339-351 
    Details
    ISSN: 0148-7280
    Schlagwort(e): spermatozoa ; flow cytometry ; DNA staining ; nuclear morphology ; ultrastructure ; mammals ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie
    Notizen: The morphological and ultrastructural changes that occur during preparation of porcine, bovine, and murine spermatozoa for flow cytometric quantification of the relative DNA content of the X- and Y-chromosome-bearing sperm populations were examined. Ejaculated spermatozoa from the boar and bull were washed using a series of dimethyl sulfoxide (DMSO) solutions prior to fixation, whereas the epididymal mouse spermatozoa were washed only in phosphate-buffered saline (PBS). Spermatozoa from all three species were then fixed in ethanol and processed for fluorochrome staining by a treatment regimen consisting of sulfhydryl reduction and proteolysis. The processed sperm nuclei were stained for DNA with the fluorochrome, 4′-6-diamidino-2-phenylindole (DAPI) before quantification by flow cytometry. Scanning and transmission electron micrographs of sperm heads taken at various steps of the preparation and staining procedures show 1) that the rigorous washing procedure disrupted the plasma and outer acrosomal membranes, 2) that ethanol fixation resulted in removal of the outer membranes and disintegration of the nuclear envelope, and 3) that thiol and proteolysis treatment removed the remaining cellular organelles including the tail and rapidly induced partial decondensation of the tightly packed chromatin. Sequential micrographs showed that the nuclear matrix of all three species increased in thickness about twofold during the preparation and staining. Consequently, the harsh procedures currently used for quantitative staining of DNA for high-resolution flow cytometric analyses destroy most cellular organelles and thereby prevent simultaneous characterization of DNA content and other sperm cell constituents.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1002/mrd.1120100402
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  • 8
    Digitale Medien
    Digitale Medien
    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
    Schlagwort(e): Heptabarbital ; heptabarbital sodium ; pharmacokinetics ; plasma concentration ; single and multiple dose kinetics ; relative bioavailability ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00614014
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  • 9
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and relative bioavailability of cyclobarbital calcium in man after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 443-450 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606563
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  • 10
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tolamolol in the treatment of hypertension (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 171-174 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609855
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