Objective The aim of the present study was to assess the possible effect of the CYP1A2 inhibitor
fluvoxamine on the disposition
of olanzapine in vivo Methods Twelve male volunteers were enrolled in the study They were assigned to two sessions with a drug free interval of at least 4 weeks All subjects received a single oral dose of olanzapine 10 mg In the control session the drug was taken alone, while in the concomitant
fluvoxamine session olanzapine was administered on the 4th day of a 9 day treatment with fluvoxamine The plasma
concentrations of olanzapine were detected by HPLC ECD Results After the co administration with fluvoxamine, mean olanzapine concentrations in plasma were increased throughout all sampling points Compared with the control session, concomitant fluvoxamine intake was associated with increased olanzapine C max (from 19 5 to 29 1 μg/L, P <0 001), a prolongation in olanzapine t 1/2 (from 32 2 to 46 1 hours, P <0 01), increased olanzapine AUC 0,120 (from 647 5 to 1 055 0 μg·h 1 ·L 1 , P <0 001); however, the olanzapine T max (from 3 8 to 2 6 hours, P <0 01), Cl s (from 16 4 to 8 5 L/h, P <0 001) and V d (from 435 5 to 299 2 L, P <0 01) were significantly reduced Conclusions Fluvoxamine markedly inhibits the metabolism of olanzapine in vivo CYP1A2 may be one of the major oxidative enzymes for the disposition of olanzapine in vivo It is recommended that the close observation and the benefit risk evaluation should be paid when the CYP1A2 involved drug is combined with olanzapine therapy