Cundy K C, Fishback J A, Shaw J P, Lee M L, Soike K F, Visor G C, Lee W A
Gilead Sciences, Inc., Foster City, California 94404.
Pharm Res. 1994 Jun;11(6):839-43. doi: 10.1023/a:1018925723889.
The bioavailability of PMEA from three oral formulations of the prodrug bis(POM)-PMEA has been evaluated in fasted male cynomolgus monkeys. The formulations examined included a hydroxypropyl-beta-cyclodextrin (HPBCD) complex, a PEG based cosolvent solution, and an aqeous suspension. Oral formulations containing 3H-bis(POM)-PMEA were compared to intravenous 3H-PMEA at 10.9 mg-eq/kg in a crossover study in four monkeys, with a 7 day washout period. No intact bis(POM)-PMEA or monoester were detected in plasma. Bioavailabilities of PMEA from the prodrug were 24.7 +/- 6.5%, 27.3 +/- 12.3% and 22.2 +/- 15.6% for the HPBCD complex, PEG solution and aqueous suspension, respectively. The oral bioavailability of PMEA from bis(POM)-PMEA was not limited by dissolution rate of the prodrug. Data for the PEG cosolvent solution and suspension indicate that the prodrug could potentially be formulated as a soft gelatin capsule or a tablet.
在禁食的雄性食蟹猴中评估了前药双（POM）-PMEA的三种口服制剂中PMEA的生物利用度。所研究的制剂包括羟丙基-β-环糊精（HPBCD）复合物、基于聚乙二醇的助溶剂溶液和水性混悬液。在一项交叉研究中，将含有3H-双（POM）-PMEA的口服制剂与静脉注射10.9毫克当量/千克的3H-PMEA在四只猴子中进行比较，洗脱期为7天。血浆中未检测到完整的双（POM）-PMEA或单酯。前药中PMEA的生物利用度对于HPBCD复合物、聚乙二醇溶液和水性混悬液分别为24.7±6.5%、27.3±12.3%和22.2±15.6%。双（POM）-PMEA中PMEA的口服生物利用度不受前药溶解速率的限制。聚乙二醇助溶剂溶液和混悬液的数据表明，前药有可能被制成软胶囊或片剂。
