Inhibition of imipramine N-demethylation by fluvoxamine in Chinese young men.
OBJECTIVE
To determine effect of fluvoxamine (Flu) on imipramine (lmi) N-demethylation in healthy Chinese subjects.


METHODS
The pharmaco-kinetic parameters of a single oral dose of lmi (100 mg) were compared before and during 2 wk coadministration of Flu (100 mg.d-1).


RESULTS
Flu resulted in a doubling of Cmax (112 +/- 33 vs 62 +/- 22 micrograms.L-1, P < 0.01) and an increase in AUC0- infinity (3.9 +/- 1.6 vs 1.5 +/- 0.6 mg.h.L-1, P < 0.01) of lmi. The T1/2 of lmi was prolonged (39 +/- 8 vs 23 +/- 7 h, P < 0.01) due to a marked reduction in Cl0 of lmi (0.6 +/- 0.3 vs 1.3 +/- 0.6 L.h-1.kg-1, P < 0.01). The Cmax of N-demethylated metabolite desipramine (Des) of lmi was decreased (10 +/- 2 vs 18 +/- 5 micrograms.L-1, P < 0.01) and AUC0- infinity of Des was reduced by 54% (0.61 +/- 0.20 vs 1.3 +/- 0.5 mg.h.L-1, P < 0.01) during coadministration with Flu.


CONCLUSIONS
Flu can markedly inhibit lmi N-demethylation in Chinese young men.
Xu
Z H
ZH
Pharmacogenetics Research Institute, Hu-nan Medical University, Changsha, China.
Huang
S L
SL
Zhou
H H
HH
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003891:Desipramine / Q000493:pharmacokinetics; D004347:Drug Interactions; D016666:Fluvoxamine / Q000494:pharmacology*; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics*; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; D016666:Fluvoxamine; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors