Transdermal Testosterone Delivery: Comparison Between Scrotal and Nonscrotal Delivery Systems

• Published in: Pharmaceutical development and technology 1999, Vol.4 (3), p.405-414
• Main Authors: Lin, Senshang, Xing, Qing-Feng, Chien, Yie W.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Area Under Curve; Biological and medical sciences; Chromatography, High Pressure Liquid; Drug Delivery Systems; General pharmacology; Hormones. Endocrine system; Kinetics; Male; Medical sciences; Nonscrotal; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Scrotal; Scrotum - metabolism; Skin Absorption; Swine; Swine, Miniature; Testosterone; Testosterone - administration & dosage; Testosterone - pharmacokinetics; Transdermal
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1081/PDT-100101376

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs), Testoderm®, designed to deliver testosterone through scrotal skin, and Androderm®, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is ∼13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg day), maximum concentration (Cmax) (54.2 versus 218.0 ng dl), and area under concentration-time curve (AUC0-28) [665 versus 3208 (ng dl) × hr] between these T-TDSs. However, there is no difference in time to reach Cmax, mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (∼13-fold) between the nonscrotal and scrotal T-TDSs.