Graves D A, Rotenberg K S, Woodworth J R, Amsel L P, Hinsvark O N
Clin Pharm. 1985 Mar-Apr;4(2):199-203.
Development of a liquid controlled-release pseudoephedrine product is described. Two bioequivalence studies were conducted. In a single-dose study involving 20 subjects, the bioavailabilities of five controlled-release suspensions with a broad range of drug-release rates were compared with an immediate-release form of pseudoephedrine hydrochloride in a four-way crossover, incomplete block, sequence-randomized study. Serial blood sampling up to 36 hours after drug ingestion provided area-under-the-curve (AUC), maximum plasma concentration (Cmax), and time to peak (tmax). In the multiple-dose study, involving 18 subjects, the bioavailability of the optimal formulation determined from the single-dose study was compared with a reference pseudoephedrine hydrochloride syrup. Serial blood sampling up to 12 hours after drug ingestion was performed to determine AUC, Cmax, and tmax. The single-dose investigation showed that all formulations were bioequivalent except the product with the slowest release rate, which had lower AUC and Cmax values. The results of the multiple-dose study confirmed these findings with the reference syrup. The use of a series of drug formulations with a wide range of release rates permitted selection of an optimal product in addition to providing the information needed to ensure continuous production of bioequivalent products.
本文描述了一种液体控释伪麻黄碱产品的研发过程。进行了两项生物等效性研究。在一项涉及20名受试者的单剂量研究中，采用四交叉、不完全区组、序列随机研究，将五种具有广泛药物释放速率的控释混悬液的生物利用度与盐酸伪麻黄碱速释剂型进行比较。在药物摄入后长达36小时进行系列血样采集，以测定曲线下面积（AUC）、最大血浆浓度（Cmax）和达峰时间（tmax）。在一项涉及18名受试者的多剂量研究中，将单剂量研究中确定的最佳制剂的生物利用度与参比盐酸伪麻黄碱糖浆进行比较。在药物摄入后长达12小时进行系列血样采集，以测定AUC、Cmax和tmax。单剂量研究表明，除释放速率最慢的产品外，所有制剂均具有生物等效性，该产品的AUC和Cmax值较低。多剂量研究结果与参比糖浆一致，证实了这些发现。使用一系列具有广泛释放速率的药物制剂，除了提供确保生物等效产品连续生产所需的信息外，还允许选择最佳产品。
