Single-dose pharmacokinetics of quetiapine in subjects with renal or hepatic impairment

1. The atypical antipsychotic quetiapine ('Seroquel'*) provides equivalent efficacy to the typical antipsychotics chlorpromazine and haloperidol in th e short-term treatment of schizophrenia. Moreover, the incidence of extrapy ramidal symptoms associated with quetiapine treatment is equivalent to that observed with placebo treatment, which may lead to increased patient compl iance with quetiapine compared with typical antipsychotics. 2. This report presents the results from two small studies aimed at determi ning the pharmacokinetics of quetiapine in nonpsychotic subjects with renal or hepatic impairment. Equal numbers of impaired subjects and healthy cont rol subjects were administered a single, 25 mg dose of quetiapine, and plas ma concentrations were determined up to 48 hr after dosing. 3. No clinically significant differences were found when the pharmacokineti c parameters for subjects with renal or hepatic impairment were compared wi th those for healthy control subjects. The results indicate that dosage adj ustment of quetiapine may be unnecessary in psychotic patients with decreas ed renal function. 4. In subjects with hepatic impairment related to alcoholic cirrhosis, the results suggest that no change is needed in the recommended quetiapine star ting dose (25 mg). However, because of a noted inter-subject variability in the clearance of quetiapine in the cirrhotic group, it is recommended that dose escalation be performed with caution in patients with hepatic impairm ent. 5. The single dose of quetiapine 25 mg generally was well tolerated in nonp sychotic subjects in good health or with either renal or hepatic impairment s. Quetiapine also had no effect on the endogenous creatinine clearance of renally impaired or healthy control subjects.