PHARMACOKINETIC EVALUATION OF ZENIPLATIN IN HUMANS

Zeniplatin, a more water-soluble organoplatinum than cisplatin, was ev aluated for clinical pharmacology in the context of a phase II trial i n previously treated patients with ovarian carcinoma. A total of 12 pa tients were given zeniplatin at 120 mg/m(2) by rapid intravenous infus ion over 90 min, with both blood and urine being sampled. All platinum moieties were analyzed in whole blood, plasma, plasma ultrafiltrate, and urine by atomic absorption, and free zeniplatin was analyzed in pl asma ultrafiltrate by specific high-performance liquid chromatography (HPLC). In a comparison of the platinum-time concentration curve, AUC (area under the curve) values indicated that approximately 90 % of pla tinum moieties were bound to circulating plasma proteins. There was no evidence of drug accumulation after repetitive dosing. The terminal h alf-life (t(1/2)) of this drug in plasma ultrafiltrate (3.7-7.2 h.) as measured by HPLC was slightly longer than that of carboplatin, wherea s total platinum moieties in plasma displayed a long t(1/2) (124-154 h ). Approximately 60 % of platinum moieties could be recovered in the u rine within 24 h. These findings suggest that zeniplatin has a pharmac okinetic profile similar to that of carboplatin.