Sathyan Gayatri, Guo Cindy, Sivakumar Krishna, Gidwani Shalini, Gupta Suneel
ALZA Corporation, Mountain View, CA, USA.
Curr Med Res Opin. 2005 Dec;21(12):1961-8. doi: 10.1185/030079905X65259.
Transdermal delivery of fentanyl has potential benefits over slow-release morphine, being largely preferred by patients owing to the combination of effective pain relief, a good safety profile and easy, pain-free dosing. The new drug-in-adhesive Durogesic D-TRANS fentanyl Matrix Delivery System (DDTDF) has improved pharmaceutical characteristics and patient acceptability compared to the original Durogesic transdermal reservoir system (fentanyl transdermal reservoir), whilst still providing reliable and consistent delivery of fentanyl. The bioequivalence of these two systems was evaluated in two studies.
Eighty healthy volunteers received single (72 h) or multiple (288 h) applications of DDTDF and the transdermal reservoir system (100 microg/h) in two separate randomised, crossover bioequivalence studies. Bioequivalence was assessed by calculating the ratio of least squares means based on log-transformed data following single system application and at steady-state during the fourth application.
Both transdermal systems were bioequivalent with respect to all tested pharmacokinetic parameters. Inter-subject variability was comparable between the two systems and was greater than intra-subject variability. Transdermal delivery was well tolerated in both groups.
The pharmacokinetic results demonstrate that DDTDF is bioequivalent to the original fentanyl transdermal reservoir system after single and multiple applications.
与缓释吗啡相比，芬太尼经皮给药具有潜在优势，因其能有效缓解疼痛、安全性良好且给药简便无痛，故而深受患者青睐。新型含药黏胶剂多瑞吉D - TRANS芬太尼基质释放系统（DDTDF）相较于原多瑞吉经皮储库系统（芬太尼经皮储库），其药学特性及患者接受度均有所改善，同时仍能可靠且持续地释放芬太尼。两项研究对这两种系统的生物等效性进行了评估。
在两项独立的随机交叉生物等效性研究中，80名健康志愿者分别单次（72小时）或多次（288小时）应用DDTDF和经皮储库系统（100微克/小时）。通过计算单次应用系统后以及第四次应用达到稳态时基于对数转换数据的最小二乘均值之比来评估生物等效性。
就所有测试的药代动力学参数而言，两种经皮系统均具有生物等效性。两种系统之间的受试者间变异性相当，且大于受试者内变异性。两组对经皮给药的耐受性均良好。
药代动力学结果表明，单次及多次应用后，DDTDF与原芬太尼经皮储库系统具有生物等效性。
