The effect of paroxetine on thiothixene pharmacokinetics
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S K Guthrie1, M Hariharan, A A Kumar
1College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
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.