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  • 1
    Electronic Resource
    Electronic Resource
    Inhibition of platelet function by a controlled release acetylsalicylic acid formulation — Single and chronic dosing studies (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 67-74 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; platelet function ; salicylate ; controlled release formulation ; single dosing ; continuous dosing ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The extent to which a controlled release acetylsalicylic acid (ASA) formulation inhibited platelet function has been evaluated in single and chronic dosing studies. In the single dose study, the platelet inhibitory effect of the controlled release formulation was compared with that of an equivalent dose of soluble ASA and an equimolar dose of sodium salicylate (SA). In the chronic dosing study, ASA dose-response curves for platelet function, including cyclooxygenase activity, were determined for various doses (20–1300 mg) of the controlled release (enteric coated pellets) ASA formulation taken by volunteers daily for one week. Platelet function was assessed by the degree of inhibition of aggregation for several aggregating agents, and the degree of inhibition of activity of platelet cyclooxygenase quantified by the estimation of malondialdehyde (MDA) production. Plasma ASA and SA concentrations were also determined in each study. The controlled release product inhibited platelet function to the same extent as an equimolar dose of soluble ASA, but did so with much lower and sometimes undetectable peak systemic plasma ASA concentrations. SA, the direct metabolite of aspirin, did not have any effect on platelet function. The ASA dose-platelet function response curves obtained from chronic dosing with the controlled release formulation appeared to be similar to those reported previously for the soluble product. The inhibition of platelet function appeared to be unrelated to plasma ASA concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395209
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  • 2
    Electronic Resource
    Electronic Resource
    Nitroglycerin disposition in human blood (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 169-175 
    Details
    ISSN: 1432-1041
    Keywords: nitroglycerin ; plasma concentration ; metabolites ; degradation ; plasma protein binding ; sample collection ; erythrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition in vitro of nitroglycerin (GTN) and its metabolites in erythrocyte suspensions, plasma and blood has been studied using labelled (3H) and unlabelled GTN and GTN metabolites separated by HPLC. GTN was rapidly metabolised (t1/2 3 min) to dinitro-metabolites and subsequently to the mononitronitrates in erythrocyte suspensions containing a therapeutic concentration of GTN (0.8–10 ng/ml). The metabolism of GTN and its dinitro-metabolites was concentration dependent. GTN and its dinitro-metabolites were plasma protein bound (11–60%). They had an apparent erythrocyte-plasma partition coefficient in the range 0.6 to 0.9. The metabolism of GTN by erythrocytes was partially inhibited by the presence of the dinitro-metabolites of GTN. The metabolism of GTN in blood samples collected from patients could be stopped by adding the collected blood to chilled tubes containing the enzyme inhibitor iodoacetamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547417
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  • 3
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 703-708 
    Details
    ISSN: 1432-1041
    Keywords: tetrabenazine ; hydroxytetrabenazine ; pharmacokinetics ; bioavailability ; active metabolite ; movement disorder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tetrabenazine and a metabolite, hydroxytetrabenazine, have been investigated in seven patients being treated for involuntary movement disorders. Tetrabenazine had a very low oral systemic availability (mean 0.049±0.032 SD). First-pass metabolism to hydroxytetrabenazine was extensive, and the systemic availability for this metabolite was high (mean 0.81±0.30 SD). Since hydroxytetrabenazine has been reported to be as active as tetrabenazine in depleting brain amines, and is present at much higher plasma concentrations than the parent drug, it is likely that this metabolite is the more important therapeutic moiety.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615962
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of posture and sleep on pharmacokinetics (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
    Details
    ISSN: 1432-1041
    Keywords: amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561587
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  • 5
    Electronic Resource
    Electronic Resource
    The effect of posture on the pharmacokinetics of intravenous benzylpenicillin (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 731-734 
    Details
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4±100.5 ml/min, 36.23±13.45 min, and 309.4±93.4 ml/min (means ± SD). The corresponding values for bedrest were 543.6±122.6 ml/min, 35.27±10.21 min, and 324.1±145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608225
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  • 6
    Electronic Resource
    Electronic Resource
    The effects of posture on the pharmacokinetics of intramuscular benzylpenicillin (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. 629-635 
    Details
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; posture ; intramuscular administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have produced conflicting results as to whether changes in posture affected the pharmacokinetics of the penicillins. We have studied the pharmacokinetics of intramuscularly administered benzylpenicillin in normal subjects during bedrest and ambulation and compared it with data obtained following intravenous administration of the same dose to the same subjects under the same conditions. The values of area under the curve, total clearance, mean residence time and renal clearance found during ambulation were 1175 (min·min·l−1), 488 (ml·min−1), 101 (min), and 264 (ml·min−1) (means). The corresponding values for bedrest were 1032 (min·mg·l−1), 544 (ml·min−1), 96.7 (min), and 315 (ml·min−1). There was a significant difference between the areas under the curve with change of posture but not between any of the other pharmacokinetic variables. The differences observed in this study are unlikely to be of clinical relevance. We suggest that the differences between the results of this study and those of previous studies may be related to the level of exercise undertaken by the subjects in the various studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542500
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  • 7
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 161-169 
    Details
    ISSN: 1432-1041
    Keywords: mebendazole ; hydatid disease ; Echinococcus granulosus ; hepatic disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of mebendazole and its metabolites have been monitored in twelve patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients; elimination half-lives ranged from 2.8–9.0 h, time to peak plasma concentration after dosing ranged from 1.5–7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCTs for the major metabolites of mebendazole (methyl 5-(α-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about five times the plasma AUCT found for mebendazole in patients on chronic therapy. It is suggested that the slower clearance of these polar metabolites relative to mebendazole results from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from two patients during surgery ranged from 59.5 to 206.6 ng/g wet weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542462
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  • 8
    Electronic Resource
    Electronic Resource
    Inhibition of platelet function by a controlled release acetylsalicylic acid formulation — Single and chronic dosing studies (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 67-74 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; platelet function ; salicylate ; controlled release formulation ; single dosing ; continuous dosing ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The extent to which a controlled release acetylsalicylic acid (ASA) formulation inhibited platelet function has been evaluated in single and chronic dosing studies. In the single dose study, the platelet inhibitory effect of the controlled release formulation was compared with that of an equivalent dose of soluble ASA and an equimolar dose of sodium salicylate (SA). In the chronic dosing study, ASA dose-response curves for platelet function, including cyclooxygenase activity, were determined for various doses (20–1300 mg) of the controlled release (enteric coated pellets) ASA formulation taken by volunteers daily for one week. Platelet function was assessed by the degree of inhibition of aggregation for several aggregating agents, and the degree of inhibition of activity of platelet cyclooxygenase quantified by the estimation of malondialdehyde (MDA) production. Plasma ASA and SA concentrations were also determined in each study. The controlled release product inhibited platelet function to the same extent as an equimolar dose of soluble ASA, but did so with much lower and sometimes undetectable peak systemic plasma ASA concentrations. SA, the direct metabolite of aspirin, did not have any effect on platelet function. The ASA dose-platelet function response curves obtained from chronic dosing with the controlled release formulation appeared to be similar to those reported previously for the soluble product. The inhibition of platelet function appeared to be unrelated to plasma ASA concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553157
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  • 9
    Electronic Resource
    Electronic Resource
    Availability of isosorbide dinitrate, diazepam and chlormethiazole, from i. v. delivery systems (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 181-185 
    Details
    ISSN: 1432-1041
    Keywords: isosorbide dinitrate ; diazepam ; chlormethiazole ; infusion systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The loss of isosorbide dinitrate from aqueous solutions stored in plastic infusion bags and/or infused through plastic giving sets was investigated. During simulated infusions, the loss of isosorbide dinitrate was found to be flow-rate dependent. The clinical and pharmacokinetic significance of this loss is discussed. Infusion of isosorbide dinitrate from a glass syringe through high density polyethylene tubing overcame the loss associated with its adinistration via plastic infusion bags and intravenous giving sets. This method was also applied successfully to minimise the previously reported loss of diazepam and chlormethiazole during infusions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561946
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 253-261 
    Details
    ISSN: 1432-1041
    Keywords: aspirin ; pharmacokinetics ; salicylate ; alcoholic liver disease ; young and elderly volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of the pharmacokinetic parameters derived from these profiles were not significantly different between young subjects, elderly subjects and subjects with alcoholic liver disease. Individual plasma albumin concentrations provided a better index of the unbound plasma salicylate clearances and salicylate plasma protein binding than the age of the subject or the presence of alcoholic liver disease. Highest unbound plasma salicylate concentrations were found in subjects with the lowest plasma albumin concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543800
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