Phase I and clinical pharmacological study of mercaptopurine administered as a prolonged intravenous infusion.

摘要: The bioavailability of oral mercaptopurine (MP) is poor, and plasma levels following p.o. dosing are highly variable. In an attempt to circumvent these problems, we conducted a Phase I trial clinical pharmacological study MP administered as prolonged i.v. infusion. An infusion rate 50 mg/sq m/h, which was designed achieve therapeutic drug in plasma, used all patients. duration escalated 12-h increments. Thirty-eight patients were evaluated. dose-limiting toxicity mucositis. Other reversible toxicities myelosuppression hepatotoxicity. 48 h found be safe, unassociated with toxicity. Objective responses seen five patients. The mean steady-state concentration achieved 6.9 µm little interpatient variability seen. Allopurinol coadministration had no effect on the pharmacokinetics MP. However, allopurinol did alter urinary metabolite pattern, decreasing thiouric acid increasing thioxanthine levels. cerebrospinal fluid:plasma ratio for 0.27, suggesting that this approach may value treatment central nervous system cancer. MP can safely 48-h at dose reliably achieves associated optimal antileukemic activity vitro .