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 paroxetine decreased the clearance of thiothixene. METHOD Ten healthy medication-free volunteers (4 women and 6 men, mean age 38 +/- 12 years) were randomized to receive a single 20 mg oral dose of thiothixene on two separate occasions. On one occasion thiothixene was given concurrently, 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 of 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 altered 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 longer paroxetine pretreatment might have caused some inhibition of thiothixene clearance.