We investigated the effect of zotepine on uric acid, xanthine and hypoxanthine in patients with schizophrenia. In addition, we performed pyrazinamide - suppression test and phenolsulfophthale in test to identify the site of its uricosuric action in the kidney.
Zotepine had a hypouricemic effect in patients with schizophrenia as reported previously, although the effect was not dose-dependent. In 6 patients treated with zotepine (40 mg/day), the serum uric acid value rose quickly one week after discontinuation of zotepine and returned close to the pretreatment level after two weeks.
Pyrazinamide blocked the uricosuric action of zotepine to the same degree as it did the uricosuric action of benzbromarone but phenolsulfophthale in excretion was not inhibited by zotepine as by benzbromarone. These findings indicate that zotepine exerts its uricosuric action at postsecretory sites. Zotepine increased the xanthine clearance/creatinine clearance ratio significantly. but decreased the hypoxanthine clearance /creatinine clearance ratio significantly. These results suggest that the renal transport mechanisms of uric acid and xanthine are similar to each other but are different from that of hypoxanthine.
