Time course of enzyme induction in humans: effect of pentobarbital on nortriptyline metabolism.

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von Bahr C, Steiner E, Koike Y, Gabrielsson J

Time course of enzyme induction in humans: effect of pentobarbital on nortriptyline metabolism.

Clin Pharmacol Ther. 1998 Jul;64(1):18-26.

PubMed ID

9695715 [ View in PubMed

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Abstract

To study the effect of induction we gave six male volunteers 10 mg nortriptyline three times a day for 4 weeks and 0.2 gm pentobarbital on days 8 to 21. Plasma and urinary levels of nortriptyline and metabolites were measured. The rate and extent of induction of the enzyme(s) were estimated by a model with use of nortriptyline concentrations. There was a marked decrease of nortriptyline levels after 2 days of pentobarbital treatment. Total clearance of nortriptyline increased more than twofold (range, 1.6-fold to 4.1-fold). Apparent metabolic clearance by 10-hydroxylation increased markedly. The decrease in nortriptyline levels was more rapid than the increase after pentobarbital cessation, fitting with the theory of the model. The induction of nortriptyline metabolism is probably mainly the result of an increase in a non-CYP 2D6 P450 isozyme, possibly CYP 3A4 or a CYP 2C form. More knowledge of induction characteristics of drugs should lead to better predictions of decreased effects and appearance of adverse effects. The kinetic model used for analysis of our data could then be useful.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Phenobarbital	Cytochrome P450 3A4	Protein	Humans	Unknown	Inducer	Details