Umstead Meghan E, Boothe Dawn M, Cruz-Espindola Crisanta, Macdonald John M, Kennis Robert, Angarano Donna
Department of Clinical Sciences, Auburn University, College of Veterinary Medicine, Auburn, AL, USA.
Vet Dermatol. 2012 Oct;23(5):431-e82. doi: 10.1111/j.1365-3164.2012.01078.x.
The prescribing of compounded products that mimic US Federal Drug Administration approved drugs in the USA is inappropriate. Among the reasons are the lack of premarket regulatory assessment and the potential for an inferior product. This study describes the accuracy and precision of ciclosporin (CsA) strength when compounded as capsules (10 and 300 mg) and solutions (50 and 150 mg/mL).
Preparation choices reflected current prescribing practices. Each was acquired by prescription from five pharmacies at three different times, 14-45 days apart. Atopica(®) (10 and 100 mg; Novartis, Greensboro, NC, USA) and three human generics (50 and 100 mg capsules and 100 mg/mL solution) were positive controls. Physical characteristics were assessed. Accuracy (percentage predicted) was based on CsA strength measured by high-performance liquid chromatography and precision was based on replications (n = 3) from each pharmacy.
Accuracy of positive controls ranged from 92 to 103%. For compounded solutions, physical characteristics differed markedly between but not within pharmacies. Capsule accuracy was 10 ± 0.98 mg (101%) for 10 mg and 290 ± 9.6 mg (97%) for 300 mg; and solution accuracy was 45 ± 9.9 mg/mL (90%) for 50 mg/mL and 127 ± 18 mg/mL (85%) for 150 mg/mL. The precision for 50 mg/mL oral solution was 0.67-11%, and for 150 mg/mL, 3.7-14%. Accuracy for all preparations varied, with the least accurate deviating by 34% from labelled strength. Precision for all capsules ranged from 0.6 to 8.7%.
Compounded CsA solutions may deviate by more than 10% from the labelled strength. Bioavailability and clinical efficacy of compounded CsA remain unknown, and such products should be prescribed only in appropriate circumstances.
在美国，开具模仿美国食品药品监督管理局批准药物的复方制剂是不合适的。原因包括缺乏上市前监管评估以及产品可能质量较差。本研究描述了环孢素（CsA）制成胶囊（10毫克和300毫克）和溶液（50毫克/毫升和150毫克/毫升）时的强度准确性和精密度。
制备选择反映了当前的处方习惯。每种制剂在三个不同时间从五家药店凭处方获取，间隔14 - 45天。Atopica（®）（10毫克和100毫克；诺华公司，美国北卡罗来纳州格林斯伯勒）和三种人用仿制药（50毫克和100毫克胶囊以及100毫克/毫升溶液）作为阳性对照。评估了物理特性。准确性（预测百分比）基于高效液相色谱法测定的CsA强度，精密度基于每家药店的重复测定（n = 3）。
阳性对照的准确性范围为92%至103%。对于复方溶液，各药店之间的物理特性差异显著，但同一药店内差异不明显。10毫克胶囊的准确性为10 ± 0.98毫克（101%），300毫克胶囊为290 ± 9.6毫克（97%）；50毫克/毫升溶液的准确性为45 ± 9.9毫克/毫升（90%），150毫克/毫升溶液为127 ± 18毫克/毫升（85%）。50毫克/毫升口服溶液的精密度为0.67%至11%，150毫克/毫升为3.7%至14%。所有制剂的准确性各不相同，最不准确的制剂与标示强度相差34%。所有胶囊的精密度范围为0.6%至8.7%。
复方CsA溶液可能与标示强度相差超过10%。复方CsA的生物利用度和临床疗效尚不清楚，此类产品应仅在适当情况下开具。
