THE EFFECT OF PAROXETINE ON THIOTHIXENE PHARMACOKINETICS

Objective: In this study healthy volunteers received thiothixene with and without a 3-day pretreatment with paroxetine to determine if parox etine decreased the clearance of thiothixene. Method: Ten healthy medi cation-free volunteers (4 women and 6 men, mean age 38 +/- 12 years) w ere randomized to receive a single 20 mg oral dose of thiothixene on t wo separate occasions. On one occasion thiothixene was given concurren tly, and following 3 days of pre-treatment with oral paroxetine (20 mg /day). On the other occasion thiothixene was given without paroxetine pre-treatment. The two study days were separated by a minimum period o f 2 weeks. On both study days, after the administration of thiothixene , 10 ml blood samples were collected over the next 72 h. Results: None of the pharmacokinetic parameters of thiothixene were significantly a ltered by a 3-day treatment with paroxetine. Discussion: It is likely that the CYP2D6 isoenzyme is not responsible for a high proportion of thiothixene clearance, but one cannot exclude the possibility that a l onger paroxetine pretreatment might have caused some inhibition of thi othixene clearance.