Viswanathan C T, Booker H E, Welling P G
J Clin Pharmacol. 1979 May-Jun;19(5-6):282-9. doi: 10.1002/j.1552-4604.1979.tb02481.x.
Serum levels of phenobarbital, and also urinary excretion of phenobarbital and p-hydroxyphenobarbital, were examined after single and repeated oral doses of phenobarbital to three male subjects. Serum levels of phenobarbital at steady state were approximately ten times as high as those after a single dose. The overall elimination rate constant for loss of phenobarbital from serum, Kel, was significantly reduced after repeated doses, and Cmax infinity values calculated from single-dose data poorly predicted observed Cmax infinity values. Five-day urinary excretion of phenobarbital and p-hydroxyphenobarbital accounted for 16 and 21 per cent, respectively, of the initial dose. Due to extensive drug accumulation, 83 per cent of the final dose was excreted in five-day urine as phenobarbital and 85 per cent, as p-hydroxyphenobarbital. Comparison of plasma and renal clearances indicated that the rate of phenobarbital metabolism was reduced owing to repeated dosing, while the rate of urinary excretion of parent drug was unchanged.
对三名男性受试者单次及重复口服苯巴比妥后，检测了其血清苯巴比妥水平以及苯巴比妥和对羟基苯巴比妥的尿排泄情况。稳态时血清苯巴比妥水平约为单次给药后的十倍。重复给药后，血清中苯巴比妥消除的总体消除速率常数Kel显著降低，根据单剂量数据计算的Cmax infinity值对观察到的Cmax infinity值预测不佳。苯巴比妥和对羟基苯巴比妥的五日尿排泄量分别占初始剂量的16%和21%。由于药物大量蓄积，最终剂量的83%以苯巴比妥形式、85%以对羟基苯巴比妥形式在五日尿中排泄。血浆清除率和肾清除率的比较表明，重复给药导致苯巴比妥代谢速率降低，而母体药物的尿排泄速率未变。
