Zeniplatin, a more water-soluble organoplatinum than cisplatin, was evaluated for clinical pharmacology in the context of a phase II trial in previously treated patients with ovarian carcinoma. A total of 12 patients were given zeniplatin at 120 mg/m2 by rapid intravenous infusion 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 plasma 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 platinum moieties were bound to circulating plasma proteins. There was no evidence of drug accumulation after repetitive dosing. The terminal half-life (t1/2) of this drug in plasma ultrafiltrate (3.7-7.2 h.) as measured by HPLC was slightly longer than that of carboplatin, whereas total platinum moieties in plasma displayed a long t1/2 (124-154 h). Approximately 60% of platinum moieties could be recovered in the urine within 24 h. These findings suggest that zeniplatin has a pharmacokinetic profile similar to that of carboplatin.
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