Scriba G K, Lambert D M, Poupaert J H
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Münster, Germany.
J Pharm Sci. 1995 Mar;84(3):300-2. doi: 10.1002/jps.2600840307.
The plasma levels of phenytoin after oral administration of phenytoin and phenytoin 2-monoglyceride, a phenytoin prodrug, to rats were determined by gas chromatography. Compared to the application of the parent drug, administration of the prodrug resulted in a 3-fold increase of Cmax and a 4-fold increase of the AUC. This correlated with an earlier onset and peaking of the anticonvulsant activity determined in the maximal electroschock (MES) test. The peak effect was reached 1 h after dosing the monoglyceride compared to 2 h after application of phenytoin itself. On the basis of the median effective dose, the prodrug was 3 times more effective antagonizing MES-induced seizures than the parent drug. It is concluded that phenytoin 2-monoglyceride might be a useful prodrug for the oral delivery of phenytoin.
通过气相色谱法测定了大鼠口服苯妥英和苯妥英前体药物苯妥英2 - 单甘油酯后的血浆苯妥英水平。与应用母体药物相比，前体药物的给药导致Cmax增加了3倍，AUC增加了4倍。这与在最大电休克（MES）试验中测定的抗惊厥活性的更早起效和达到峰值相关。给药单甘油酯后1小时达到峰值效应，而应用苯妥英本身后则为2小时。基于半数有效剂量，前体药物拮抗MES诱导的癫痫发作的效果是母体药物的3倍。得出的结论是，苯妥英2 - 单甘油酯可能是苯妥英口服给药的一种有用的前体药物。
