正常人口服单剂量和多剂量地尔硫的药代动力学研究

THE PHARMACOKINETICS OF DILTIAZEM AFTER SINGLE AND MULTIPLE DOSING IN NORMAL VOLUNTEERS

８名健康者，随机交叉口服两种单剂量（３０ｍｇ）地尔硫普通片后，利用ＨＰＬＣ法测定血浆中地尔硫，其药代动力学过程均符合二室开放模型，消除半衰期分别为３．６±３．５和４．７±１．８ｈ。分别在３．１±０．４和３．１±０．２ｈ达到峰值１１８．５±１４．３和１１３．０±３２．０μｇ／Ｌ，血药浓度曲线下面积分别为７９３．１±８３．１和７４７．５±１２１．５μｇ·ｈ·Ｌ－１。８名健康者，随机交叉口服两种多剂量（每次３０ｍｇ，８ｈ一次）地尔硫普通片后，测得两种片剂稳态时的Ｃｍａｘ分别为８５．４±１９．８和９１．１±２８．４μｇ／Ｌ，Ｃｍｉｎ分别为３０．７±９．２和２９．０±７．７μｇ／Ｌ。两者的血药浓度波动系数ＦＩ分别为０．９１±０．４０和１．００±０．２９。经双单侧Ｔ检验法检验，两种片剂具有生物等效性。

The pharmacokinetics and relative bioavailability of two formulations of diltiazem were determined following a single and multiple oral dose of diltiazem given to normal volunteers in an open randomized crossover study. After a single oral dose the peak levels in plasma averaged 118.5±14.3 and 113.0±32.0 μg/L at 3.1±0.4 and 3.1±0.2 h and the areas under the drug concentration curves were 793.1±83.1and 747.5±121.5 μg·h·L-1 for reference and testing tablet, respectively.The bioavailability for the testing tablet was 94.4±12.5%.Following multiple dosing mean steady state Cmax values were 85.4±19.8 and 91.1±28.4 μg/L and mean Cmin values were 30.7±9.2 and 29.0±7.7 μg/L for testing and reference tablet, respectively. The peak-to-trough fluctuation index (FI) for the two formulations were 0.91±0.40 and 1.00±0.29, respectively. The result of two one-sided tested showed that the two formulations were bioequivalence.