Effect of dose on phenytoin absorption.
Effect of dose on phenytoin absorption.
复制标题
剂量对苯妥英吸收的影响。
DOI：
10.1038/clpt.1980.191
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发表时间：
1980
影响因子：
6.7
通讯作者：
Perrier,D
中科院分区：
文献类型：
--
作者：
Jung,D;Powell,JR;Walson,P;Perrier,D
为确定剂量对苯妥英生物利用度的影响，6例健康男性受试者接受15 mg/kg单次静脉给药，400、800和1，600 mg单次口服给药，以及1，600 mg分次给药（每3小时400 mg）。使用静脉给药的Vmax（最大消除速率）和Km（消除速率为最大速率一半时的血清浓度）值确定吸收程度。虽然未检测到苯妥英吸收程度的统计学显著性差异，但达到苯妥英最大血清浓度的时间从400 mg剂量的8.4小时和800 mg剂量的13.2小时增加至1，600 mg剂量的31.5小时。400、800和1，600 mg剂量以及1，600 mg分次给药后，血清浓度峰值分别为3.9、5.7、10.7和15.3 mg/l。这表明，延长，但完全吸收大剂量的苯妥英是由于缓慢溶解和持续吸收的结肠。由于苯妥英的吸收延长，可能需要使用比静脉内负荷剂量更大的口服负荷剂量，以达到相同的最大苯妥英血清浓度。
To determine the effect of dose on phenytoin bioavailability, a single intravenous 15‐mg/kg dose, single oral doses of 400, 800, and 1,600 mg, and 1,600 mg in divided doses (400 mg every 3 hr) were given to six healthy male subjects. Values of Vmax(maximum elimination rate) and Km(serum concentration at which rate of elimination is one half the maximum rate) from the intravenous dose were used to determine the extent of absorption. Although no statistically significant difference in extent of phenytoin absorption was detected, the time to reach maximum phenytoin serum concentrations increased from 8.4 hr for the 400‐mg dose and 13.2 hr for the 800‐mg dose to 31.5 hr for the 1,600‐mg dose. After the 400, 800, and 1,600‐mg doses and 1,600‐mg divided doses, the serum concentration peaks were 3.9, 5.7, 10.7, and 15.3 mg/l. It is suggested that the prolonged, but complete, absorption of large phenytoin doses is due to slow dissolution and continued absorption from the colon. Due to prolonged absorption of phenytoin, it may be necessary to use larger oral than intravenous loading doses to achieve the same maximum phenytoin serum concentrations.Clinical Pharmacology and Therapeutics(1980)28,479–485; doi:10.1038/clpt.1980.191