| pA2 online © Copyright 2004 The British Pharmacological Society |
164P
University of Newcastle Winter Meeting December 2004 |
Pharmacokinetic study of the transdermal delivery system, TDS© -testosterone in healthy subjects Z.Chik1, A. Johnston1, A.T. Tucker1,2, S. L. Chew 4 & C. A. S. Alam5. 1Clinical Pharmacology, 5Experimental Pathology, William Harvey Research Institute, Barts and The London Queen Mary’s School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, 2The Ernest Cooke Clinical Microvascular Unit, 3Anaesthetics and 4Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE. |
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Print abstractA new formulation to deliver testosterone via the transdermal route was developed and tested. The TDS© preparation is a liquid formulation which can be applied on the skin via a metered pump spray to deliver a drug through the skin. The aim of this study was to assess the capability of the TDS© preparation to deliver testosterone systemically and to obtain the pharmacokinetic profiles of testosterone. An open label, comparative, randomized placebo controlled study involving three treatments and three-periods was conducted. Twelve healthy volunteers have received 50 mg TDS©-Testosterone, TDS©-Placebo, and 50 mg of a commercially available topical testosterone preparation (Androgel®, 1% topical testosterone gel). Blood samples were obtained from 30 min before dosing, prior to dosing (0 h) and up to 24 h post-dosing. From the blood concentration profiles, the AUC and Cmax values were calculated for both 0–12 and 0–24 h.
The average AUC(0,12 h) was higher following application of TDS©-Testosterone compared with Androgel® and TDS©-Placebo with values of 61.8, 57.7, and 50.7 ng ml-1 h, for TDS©-Testosterone, Androgel®, and TDS placebo, respectively. However, the average AUC(0,24 h) for Androgel® was higher than TDS©-Testosterone and TDS©-Placebo with values of 135.8, 157.4, and 101.7 ng ml-1 h, for TDS©-Testosterone, Androgel®, and TDS©-Placebo, respectively. The average Cmax (0,12 h) was similar for TDS©-Testosterone (6.6 ng ml-1) and Androgel® (6.5 ng ml-1) and higher than for TDS©-Placebo (5.7 ng ml-1). Due to the higher 24 h concentrations of testosterone in a few subjects, the average Cmax (0,24 h) value for Androgel® was very high compared with TDS©-Testosterone and TDS©-Placebo with values of 13.7, 8.4, and 5.9 ng ml-1, respectively.
Analysis of variance ( anova) showed that the 90% confidence interval of the AUC(0,12 h) and the Cmax (0,12 h) were contained within the bioequivalence limit (80 – 125%) for TDS©-Testosterone vs Androgel®, Cmax 89.2 to 112.3% and AUC 93.5 to 120.5%. The serum testosterone concentrations were lower following TDS©-Placebo and were not bioequivalent with either formulation.
Hence the TDS© preparation can deliver testosterone systemically in humans and the concentrations of hormone in the first 12 h following TDS© administration are bioequivalent to an existing topical delivery gel.