摘要:

AbstractThe hydrolysis of diltiazem in biological fluids: whole blood, plasma, and gastric fluid was investigated under conditions considered close to the physiological situation. The most significant rate of hydrolytic degradation was found in whole blood (half‐life of 27h), followed by plasma (half‐life of 88h), while the least significant degradation rate was observed in gastric fluid (half‐life 153h). The kinetic profiles of diltiazem hydrolysis indicate that hydrolytic degradation in the biological fluids makes a minimal contribution to the clearance and disposition of the

ISSN:0142-2782    

DOI:10.1002/bdd.2510120502

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractA method for calculating the mean residence times of metabolites in the body, systemic circulation, and peripheral tissue is described. The calculations require the AUC, AUMC, and derivatives of the plasma concentration versus time curves of the metabolite and its precursor. The method is applicable to metabolites with any precursor order and does not require separate administration of the metabolite. The approach is applied to published data for the primary and secondary metabolites of ketamine.

ISSN:0142-2782    

DOI:10.1002/bdd.2510120503

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractA method to quantitateN‐acetylcysteine in plasma using reductive cleavage with tributyl‐phosphine and post‐HPLC column derivatisation witho‐phthalaldehyde is described. Using this method, endogenous average concentrations of 0·08 μM were measured in 10 volunteers participating in a crossover study to compare the bioavailability of two different formulations ofN‐acetylcysteine. The drug was detected in plasma for up to 12h after administration of a single oral dose (200 mg); theCmaxvalues were up to 20 times the endogenous levels. The sensitivity and selectivity of the method should thus enable the behaviour ofN‐acetylcysteine after oral administration to be properly described and bioavailability studies to

ISSN:0142-2782    

DOI:10.1002/bdd.2510120504

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThein vivocharacteristics of two formulations of a recently developed controlled‐release system, the Gradient Matrix System (GMS‐1 and GMS‐2), with acetaminophen as a model drug compound have been determined in healthy volunteers both after separate single‐ and multiple‐dose administration. Values for the mean residence time (MRT) were increased from 5·2 h for an oral solution to 10·2 and 13·3 h for two GMS formulations after single dosing. Peak plasma concentrations were lower for the two GMS formulations after single dosing compared to the oral solution. The bioavailability, relative to the oral solution, was 91 per cent and 84 per cent for the two GMS formulations tested. After multiple dosing of one of the GMS formulations over 5 days, no change in AUC compared to the single dose AUC occurred. Steady state was reached within 2–3 days of twice daily dosing of the GMS formulation. The peak‐trough‐fluctuation (per cent PTF) was 44 per cent. No signs of dose dumping were observed in fasted subjects. A plateau‐like plasma drug concentration profile at steady state was maintained with

ISSN:0142-2782    

DOI:10.1002/bdd.2510120505

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractAn effort was made to correlate thein vivoandin vitrorelease data of acetaminophen from two formulations of a recently developed controlled‐release system, the Gradient Matrix System (GMS‐1 and GMS‐2). Thein vivorelease curves, obtained by deconvolution of the plasma concentration time plots, showed a small inter‐subject variability. GMS‐1 with fastestin vitrorelease also showed fastestin vivorelease. A good relationship was only found after time‐scaling of the r

ISSN:0142-2782    

DOI:10.1002/bdd.2510120506

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractHealthy volunteers received intravenous and/or oral doses of sodium dichloroacetate (DCA) in various single and multiple dose regimens. A crossover bioavailability study proved abortive because second and subsequent doses showed significantly longer terminal elimination half‐lives (means 3·64 h and 9·9 h, respectively) than was the case for initial doses (1·58 h). A parallel bioavailability comparison failed to show that oral doses were significantly different from 100 per cent bioavailability (AUCoral, 604μgh−1ml−1; AUCi.v., 489μgh−1ml−1). The time required to elapse between individual doses, in order to prevent second doses having relatively long half‐life values, varied in different individuals from 1 week to greater than 3 months. No cardiac or central nervous system effects were recorded by echocardiography and digit symbol substitution tests, respectively. The mean renal clearance of DCA was 42·9 ml h−1. No differences were observed in DCA kinetics between male

ISSN:0142-2782    

DOI:10.1002/bdd.2510120507

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractDiltiazem undergoes extensive first‐pass metabolism; extrapolation from single to repeated administration thus underestimates plasma concentration values. In order to validate the hypothesis of a partially saturable first‐pass effect, four single doses of diltiazem (10, 20, 40, and 120 mg) were administered at weekly intervals to eight healthy volunteers. Results showed that: (a) the inter‐subject variability was highest at the lowest dose and lowest at the highest dose; (b) bioavailability was almost nil in 3 of 8 of the subjects after the administration of the 10 mg dose; (c) the mean bioavailability increased with the dose from 11·8 ± 2·5 per cent after 10 mg to 28·2 per cent after 120 mg; (d) the elimination half‐life was dose‐related; (e) the renal excretion of diltiazem increased with the administered dose from 1.0 ± 0·3 per cent after 10 mg to 3·0 ± 0·5 per cent after 120 mg; (f) the greatest amounts of circulating metabolites were present after the lowest doses. These results are consistent with a partially saturable first‐pass

ISSN:0142-2782    

DOI:10.1002/bdd.2510120508

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510120501

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY