Lack of change in fluoxetine and norfluoxetine kinetics when switching from fluoxetine to paroxetine

Pharmacokinetic interactions are possible with the prescription of two or more psychotropics. This caution could also apply to the proximal use of selective serotonin (5-hydroxytryptamine) re-uptake inhibitors (SSRIs), especially those that may be potent inhibitors of specific hepatic metabolizing enzyme systems. Both fluoxetine (FLX) and paroxetine (PAR) are inhibitors of the cytochrome P4502D6 enzyme system. In order to assess the potential pharmacokinetic interactions between these two SSRIs, nine patients were first treated with fixed therapeutic doses of FLX for a minimum of 6 weeks. Subsequently, in a double-blind design, some of these patients were abruptly switched to PAR, 20 mg/day, and others were switched to placebo. Serum levels of FLX, norfluoxetine (NFLX), and PAR were collected before and at specific points after the switch. The results suggest that the clearance kinetics of FLX and NFLX are not affected by the abrupt switch to PAR. It was not possible to determine whether the kinetics of PAR were influenced by the residual FLX and NFLX concentrations.