Terhaag B, Donath F, Le Petit G, Feller K
Int J Clin Pharmacol Ther Toxicol. 1986 Jun;24(6):298-302.
The in vitro liberation and the bioavailability (BV) of dipyridamole (D) in three different brands (A, B, C) were determined in a three way cross-over study on 12 healthy subjects. Also, the pharmacokinetics of D given intravenously was investigated. The in vitro liberation of B is only to be achieved by repeated touching. The tmax for the preparations, expressed as mean +/- s mean amounts as follows: A: 0.8 +/- 0.06; B: 1.1 +/- 0.1; C: 0.8 +/- 0.09 hours and is in the case of B significantly different (p less than 0.05) from the others. The cmax values (A: 1.01 +/- 0.25; B: 1.16 +/- 0.15; C: 1.51 +/- 0.3 mumol X l-1) and the AUC values (A: 3.8 +/- 0.9; B: 3.1 +/- 0.5; C: 3.8 +/- 0.7 mumol X h X l-1) are not different. The absolute BV of D is 27 +/- 5.5% (range: 11-44%) independent of the used brand. In 4 subjects a second tmax at the 4th-6th hour is to be observed irrespective of the way of dosing. An enterohepatic circulation is assumed. It is concluded that the determination of the in vitro liberation is a necessary and useful parameter, but cannot be used alone for characterization of the BV in every case, as e.g., for problem drugs.
在一项针对12名健康受试者的三交叉研究中，测定了三种不同品牌（A、B、C）双嘧达莫（D）的体外释放度和生物利用度（BV）。此外，还研究了静脉注射D的药代动力学。B的体外释放仅通过反复接触才能实现。制剂的达峰时间（tmax），以平均值±标准差表示如下：A：0.8±0.06；B：1.1±0.1；C：0.8±0.09小时，其中B与其他品牌有显著差异（p<0.05）。峰浓度（cmax）值（A：1.01±0.25；B：1.16±0.15；C：1.51±0.3μmol·L⁻¹）和曲线下面积（AUC）值（A：3.8±0.9；B：3.1±0.5；C：3.8±0.7μmol·h·L⁻¹）无差异。D的绝对生物利用度为27±5.5%（范围：11-44%），与使用的品牌无关。在4名受试者中，无论给药方式如何，在第4至6小时都可观察到第二个达峰时间。推测存在肠肝循环。得出的结论是，体外释放度的测定是一个必要且有用的参数，但在每种情况下，例如对于有问题的药物，不能单独用于表征生物利用度。
