Pharmacokinetics of RK-28 (a New Radiosensitizer) and Pharmaceutical Design of a Suppository Form Using Rats

概要

論文の詳細を見る
The pharmacokinetics of RK-28,a new hypoxic cell radiosensitizer, was studied in rats following its intravenous, intraportal, oral, and rectal administration. The pharmaceutical design of an RK-28 suppository form was also examined. After intravenous injection, RK-28 was rapidly removed from the plasma (biological half-life of 17 min) and its area under the curve (AUC) was proportional to the amount of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for intraportal administration and 36.9% for oral administration. Following oral administration of RK-28,it seems likely that specific acid-catalyzed decomposition of RK-28 takes place in the stomach and then the absorbed RK-28 undergoes first-pass metabolism in the liver. When "solidified RK-28 suppository, " made by solidifying molten RK-28,was inserted into the rectum, hepatic first-pass metabolism could be avoided substantially. The resulting absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion suppository, " prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80℃, showed a plasma concentration-time curve very suitable for radiation therapy; the maximum plasma concentration was attained 30 min after rectal administration and then decreased within a short period. Administration of "RK-28 emulsion suppository, " resulted in an absolute bioavailability of 76%.
社団法人日本薬学会の論文
1994-01-15