Colucci R D, Scavone J M, Auty R, Glassner-Cohen L
Clinical Pharmacology/Clinical Research, Schering-Plough Research, Institute Kenilworth, NJ 07033.
Int J Clin Pharmacol Ther. 1994 Jan;32(1):24-5.
Microdose (1 mg) captopril therapy is commonly used for the initial dose titration in patients with congestive heart failure. Since this dosage form is not commercially available, it has to be extemporaneously compounded. Quality control of each batch is commonly evaluated using the weight variation technique described in the USP. Despite careful titration with microdose, captopril capsules variability in patient's response has been observed. In order to explain this fluctuation, the actual content of extemporaneously compounded microdose captopril capsules was evaluated using a high pressure liquid chromatographic assay. Microdose captopril capsules were prepared by triturating 25 mg tablets with lactose in a mortar using standard geometric dilution technique and a Sharpe-Dohme hand-operated capsule filling machine. Forty-eight microdose captopril capsules were randomly selected from the compounded batch and were individually assayed for captopril amount. The mean +/- standard deviation (SD) amount of captopril in each capsule was 1.27 g +/- 0.31 mg with a range of 0.84 g to 1.96 mg. The coefficient of variation was 24.5%. Ten captopril capsules were randomly selected from the compounded batch and were individually weighed. The capsules had a mean weight +/- SD of 198.3 g +/- 21.2 mg and a coefficient of variation of 7.3%. Even though the extemporaneously prepared microdose captopril capsules were within acceptable limits for weight variation described in the USP, the actual dose administered to the patients could vary by as much as 24.5%.
小剂量（1毫克）卡托普利疗法常用于充血性心力衰竭患者的初始剂量滴定。由于这种剂型没有商业供应，必须临时配制。每批产品的质量控制通常采用美国药典中描述的重量差异技术进行评估。尽管使用小剂量进行了仔细滴定，但仍观察到卡托普利胶囊在患者反应方面存在变异性。为了解释这种波动，使用高压液相色谱分析法对临时配制的小剂量卡托普利胶囊的实际含量进行了评估。小剂量卡托普利胶囊是通过使用标准几何稀释技术在研钵中将25毫克片剂与乳糖研磨，并使用夏普-多姆手动胶囊填充机制备而成。从配制批次中随机选取48粒小剂量卡托普利胶囊，并分别测定其中卡托普利含量。每粒胶囊中卡托普利的平均含量±标准差（SD）为1.27克±0.31毫克，范围为0.84克至1.96毫克。变异系数为24.5%。从配制批次中随机选取10粒卡托普利胶囊并分别称重。这些胶囊的平均重量±SD为198.3克±21.2毫克，变异系数为7.3%。尽管临时制备的小剂量卡托普利胶囊的重量差异在USP规定的可接受范围内，但给予患者的实际剂量可能相差多达24.5%。
