TIME-COURSE OF ENZYME-INDUCTION IN HUMANS - EFFECT OF PENTOBARBITAL ON NORTRIPTYLINE METABOLISM

Citation
C. Vonbahr et al., TIME-COURSE OF ENZYME-INDUCTION IN HUMANS - EFFECT OF PENTOBARBITAL ON NORTRIPTYLINE METABOLISM, Clinical pharmacology and therapeutics, 64(1), 1998, pp. 18-26
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
0009-9236
Volume
64
Issue
1
Year of publication
1998
Pages
18 - 26
Database
ISI
SICI code
0009-9236(1998)64:1<18:TOEIH->2.0.ZU;2-F
Abstract
To study the effect of induction we gave six male volunteers 10 mg nor triptyline three times a day for 4 weeks and 0.2 gm pentobarbital on d ays 8 to 21, Plasma and urinary levels of nortriptyline and metabolite s were measured. The rate and extent of induction of the enzyme(s) wer e estimated by a model with use of nortriptyline concentrations, There was a marked decrease of nortriptyline levels after 2 days of pentoba rbital treatment. Total clearance of nortriptyline increased more than twofold (range, 1.6-fold to 4.1-fold). Apparent metabolic clearance b y 10-hydroxylation increased markedly. The decrease in nortriptyline l evels was more rapid than the increase after pentobarbital cessation, fitting with the theory of the model, The induction of nortriptyline m etabolism is probably mainly the result of an increase in a non-CYP 2D 6 P450 isozyme, possibly CYP 3A4 or a CYP 2C form, More knowledge of i nduction characteristics of drugs should lead to better predictions of decreased effects and appearance of adverse effects. The kinetic mode l used for analysis of our data could then be useful.