Effect of troleandomycin on the pharmacokinetics of imipramine in Chinese: the role of CYP3A

• Published in: British journal of clinical pharmacology 1997-08, Vol.44 (2), p.195-198
• Main Authors: Wang, Jun‐Sheng, Wang, Wei, Xie, Hong‐Guang, Huang, Song‐Lin, Zhou, Hong‐Hao
• Format: Article
• Language: English
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; Antidepressive Agents, Tricyclic - blood; Antidepressive Agents, Tricyclic - pharmacokinetics; Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; China; CYP3A; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - metabolism; desipramine; Enzyme Inhibitors - pharmacology; Humans; imipramine; Imipramine - blood; Imipramine - pharmacokinetics; Male; Medical sciences; Methylation; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Neuropharmacology; Original; Oxidoreductases, N-Demethylating - antagonists & inhibitors; Oxidoreductases, N-Demethylating - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reference Values; Troleandomycin; Troleandomycin - pharmacology
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.1997.00649.x

Aims In vitro data indicate that imipramine (IMI), a widely used tricyclic antidepressant drug, is N‐demethylated by several isoforms of cytochrome P450, which include CYP3A4. The aim of this study was to investigate the role of CYP3A in the in vivo N‐demethylation of IMI. Methods Healthy subjects were given troleandomycin (TAO), a selective inhibitor of CYP3A, 250 mg daily for 2 days before a single oral dose of 100 mg IMI was administered. Results Pretreatment with TAO significantly increased the AUC of IMI by 59% (1971±938 vs 3134±2000 μg l−1 h, 95% confidence interval for difference between means: 218 to 2108 μg l−1 h, P