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

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<0.05) and decreased its oral clearance by 30% (60.9±27.4 vs 42.5±22.7 l h−1, 95% confidence internal for difference between means: 7.2 to 31.7 l h−1, P<0.05). Conclusions We conclude that CYP3A may play an important role in the in vivo N-demethylation of IMI.