Pharmacokinetics of a new testosterone transdermal delivery system, TDS®-testosterone in healthy males
Pharmacokinetics of a new testosterone transdermal delivery system, TDS®-testosterone in healthy males
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DOI：
10.1111/j.1365-2125.2005.02542.x
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发表时间：
2006-03-01
影响因子：
3.4
通讯作者：
Alam, CAS
中科院分区：
文献类型：
--
作者：
Chik, Z;Johnston, A;Alam, CAS
目的透皮给药系统(TDS(R))是一种液体制剂，可通过计量泵喷雾将药物输送到体循环。本研究的目的是系统地评估TDS(R)制剂传递睾酮的能力，并描述该激素在健康男性体内的药代动力学特征。方法采用开放标签、比较、随机、安慰剂对照研究，包括三个疗程，至少一个洗脱期。12名健康男性服用50 mg TDS(R)-睾酮，TDS(R)-安慰剂，以及50 mg市售睾酮制剂(安德罗凝胶(R)，1%局部睾酮凝胶)。结果使用TDS(R)-睾酮后，平均AUC(0，12h)更高(61.8ngml(-1)h)，TDS(R)-睾酮(6.6 ng ml(-1))和安慰剂(TDS(R))(6.5ngml(-1))的平均C-max(0，12h)相似，高于TDS(R)-安慰剂(5.7 ng ml(-1))。方差分析显示，TDS(R)-睾酮与安慰剂(R)的AUC(0，12 h)和C-max(0，12 h)的相对差值的90%可信区间在生物等效性限值(80,125%)内(C-max 89.2,112.3%和AUC93.5,120.5%)。服用TDS(R)安慰剂后，血清睾酮浓度较低，且与凝胶或喷雾剂均不具有生物等效性。结论TDS(R)制剂可系统地将睾酮释放到人体内，TDS(R)给药后12h内的激素浓度与现有的局部给药凝胶相当。
AimsThe Transdermal Delivery System (TDS (R)) is a liquid formulation that can be applied to the skin via a metered pump spray to deliver drug to the systemic circulation. The aims of this study were to assess the ability of the TDS (R) preparation to deliver testosterone systemically, and to characterize the pharmacokinetic profiles of the hormone in healthy males.MethodsAn open label, comparative, randomized placebo controlled study involving three treatments and three periods with a minimum of a 1 week washout period was conducted. Twelve healthy males received 50 mg TDS (R)-testosterone, TDS (R)-placebo, and 50 mg of a commercially available topical testosterone preparation (Androgel((R)), 1% topical testosterone gel).ResultsThe mean AUC(0,12 h) was higher following application of TDS (R)-testosterone (61.8 ng ml(-1) h), compared with Androgel((R)) (57.7 ng ml(-1) h) and TDS (R)-placebo (50.7 ng ml(-1) h. The mean C-max (0,12 h) was similar for TDS (R)-testosterone (6.6 ng ml(-1)) and Androgel((R)) (6.5 ng ml(-1)) and these values were higher than those for TDS (R)-placebo (5.7 ng ml(-1)). Analysis of variance showed that the 90% confidence intervals on the relative difference of the ratio for the AUC(0,12 h) and the C-max (0,12 h) between TDS (R)-testosterone and Androgel((R)), were contained within the bioequivalence limit (80, 125%) (C-max 89.2, 112.3% and AUC 93.5, 120.5%). Serum testosterone concentrations were lower following TDS (R)-Placebo and were not bioequivalent either to the gel or spray.ConclusionsThe TDS (R) preparation was shown to deliver testosterone systemically to humans and the concentrations of the hormone in the 12 h following TDS (R) administration were bioequivalent to an existing topical delivery gel.