正常人口服单剂量和多剂量尼卡地平的相对生物利用度研究

STUDY ON THE RELATIVE BIOAVAILABILITY OF NICARDIPINE AFTER SINGLE AND MULTIPLE DOSING IN NORMAL VOLUNTEERS

１０名健康者，随机交叉口服单剂量（４０ｍｇ）尼卡地平普通片和缓释片后，利用ＨＰＬＣ法测定血浆中尼卡地平浓度，分别在１．６±０．３和３．５±０．２ｈ达到峰值１０９．８±３８．７和６３．１±１４．６μｇ·Ｌ－１，血药浓度曲线下面积分别为３５０．９±７２．３和３８９．６±８０．４μｇ·ｈ·Ｌ－１。１０名健康者，随机交叉口服多剂量尼卡地平普通片（每次２０ｍｇ，８ｈ一次）和尼卡地平缓释片（每次４０ｍｇ，１２ｈ一次）后，测得两种片剂稳态时的Ｃｍａｘ分别为７４．２±１５．８和８５．３±１８．９μｇ·Ｌ－１，Ｃｍｉｎ分别为９．４±２．４和１２．１±２．６μｇ·Ｌ－１。两者的血药浓度波动系数ＦＩ分别为１．５４±０．１２和１．４９±０．１１。经双单侧Ｔ检验法检验，两种片剂血药浓度曲线下面积具有等效性。

The pharmacokinetics and relative bioavailability of a sustained-released formulation of nicardipine was determined following a single and multiple oral dose of nicardipine given to normal volunteers in an open randomized crossover study. After a single oral dose the peak levels in plasma averaged 109.8±38.7 and 63.1±14.6 μg·L-1 at 1.6 ±0.3 and 3.5±0.2 h and the areas under the drug concentration curves were 350.9±72.3 and 389.6±80.4 μg·h·L-1 for conventionl formulation and sustained-released formulation, respectively. The bioavailability for the sustained-released formulation was 111.4±10.3 %. Following multiple dosing mean steady state Cmax values were 74.2±15.8 and 85.3±18.9 μg·L-1 and mean Cmin values were 9.4±2.4 and 12.2±2.6 μg·L-1 for conventionl formulation and sustained-released formulation, respectively. The peak-to-trough fluctuation index (FI) for the two formulations were 1.54±0.12 and 1.49±0.11, respectively. The results of two one-sided tests showed that the two formulations were bioequivalent.