[en] The present study assessed pharmacokinetic testosterone time profile and dose proportionality after application of a new matrix testosterone patch (30, 45, and 60 cm2 containing 0.5mg of testosterone per cm2). This open study was a single dose, three-period, crossover trial with a randomised treatment sequence in 24 hypogonadal men, consisting in a single 48-h application of two patches of 2x 30 cm2, 2x 45 cm2, 2x 60 cm2, separated by a 5-day wash-out. Testosterone concentrations were determined during patch application and after patch removal. Dose proportionality was assessed on baseline corrected, dose normalised parameters for C av,corr/D, C max,corr/D and AUC(0-48),corr/D. Testosterone concentrations rose during the first 9h following patch application, remained relatively sustained until 48 h and then decreased abruptly after patch removal, with a half-life of 1.3h. Testosterone levels were maintained above 3 ng/mL for 42-45 h with all patches. C av were 3.39, 4.03 and 4.58 ng/mL and Cmax were 4.33, 5.29 and 6.18 ng/mL according to the doses. AUC 0-48), C av and Cmax were dose dependent with mean ratios within the acceptance range (0.70-1.43). In conclusion, dose linearity was demonstrated between the different strengths of testosterone patches. Application resulted in dose proportional increases in serum T levels in hypogonadal men into the low to mid-normal range within the first hours and achieved steady state for 48 h. During this short term study with three consecutive patch applications, this patch was shown to be efficient, convenient and safe with excellent adhesiveness and skin tolerability, and with no cross-contamination to partner or to environment.
Jeffcoate S.L., Brooks R.V., Lim N.Y., London D.R., Prunty F.T., and Spathis G.S. Androgen production in hypogonadal men. J. Endocrinol. 37 (1967) 401-411
Dobs A.S., Meikle A.W., Arver S., Sanders S.W., Caramelli K.E., and Mazer N.A. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J. Clin. Endocrinol. Metab. 84 (1999) 3469-3478
Bain J. Male hypogonadism. Comp. Ther. 9 (1983) 17-24
Meikle A.W., Mazer N.A., Moellmer J.F., Stringham J.D., Tolman K.G., Sanders S.W., and Odell W.D. Enhanced transdermal delivery of testosterone across non scrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J. Clin. Endocrinol. Metab. 74 (1992) 623-628
Wang C., Swerdloff R.S., Iranmanesh A., Dobs A., Snyder P., Cunningham G., and Matsumoto A. Transdermal testosterone gel improves sexual function, mood, muscle strength and body composition parameters in hypogonadal men. J. Clin. Endocrinol. Metabol. 85 (2000) 2839-2853
Johnsen S.G., Benett E.P., and Jensen V.G. Therapeutic effectiveness of oral testosterone. Lancet 2 (1974) 1473-1475
Ross R.J., Jabbar A., Jones T., Roberts B., Dunkley K., Hall J., Long A., Levine H., and Cullen D. Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in hypogonadal men. Eur. J. Endocrinol. 150 (2004) 57-63
Stuenkel C.A., Dudley R.E., and Yen S.S. Sublingual administration of testosterone-hydroxypropyl-beta-cyclodextrin inclusion complex stimulates episodic androgen release in hypogonadal men. J. Clin. Endocrinol. Metabol. 72 (1991) 1054-1059
Matsumoto A.M. Hormonal therapy of male hypogonadism. Endocrinol. Metab. Clin. North Am. 23 (1994) 857-875
Handelsman D.J., Conway A.J., and Boyla L.M. Pharmacokinetics and pharmacodynamics of testosterone pellets in man. J. Clin. Endocrinol. Metab. 71 (1990) 216-222
Korenman S.G., Viosca S., Garza D., Guralnik M., Place V., Campbell P., and Davis S.S. Androgen therapy of hypogonadal men with transcrotal testosterone systems. Am. L. Med. 83 (1987) 471-478
Wang C., Berman N., Longstreth J.A., Chuapoco B., Hull L., Steiner B., Faulkner S., Dudley R.E., and Swerdloff R.S. Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. J. Clin. Endocrinol. Metab. 85 (2000) 964-969
Swerdloff R.S., Wang C., Cunningham G., Dobs A., Iranmanesh A., Matsumoto A.M., Snyder P.J., Weber T., Longstreth J., and Berman N. Long-term Pharmacokinetics of transdermal testosterone gel in hypogonadal men. J. Clin. Endocrinol. Metab. 85 (2000) 4500-4510
Chik Z., Johnston A., Tucker A., Chew S.L., Mickaels L., and Alam C. Pharmacokinetics of a new testosterone transdermal delivery system, TDS-testosterone in healthy males. Br. J. Clin. Pharmacol. 10 (2005) 1-5
Westaby D., Ogle S., Paradinas F., Randell J., and Murray-Lyon I. Liver damage from long-term methyltestosterone. Lancet 2 (1977) 262-273
Brocks D.R., Meikle A.W., Boike S.C., Mazer N.A., Zariffa N., Audet P.R., and Jorkasky D.K. Pharmacokinetics of testosterone in hypogonadal men after transdermal delivery: influence of dose. J. Clin. Pharmacol. 36 (1996) 732-739
In: Gibaldi M., Perrier D., and Dekker (Eds). Pharmacokinetics (2nd edition revised and expanded) vol. 15 (1982), Drugs and Pharmaceutical Sciences, New York
In: Rowland M., and Tozer T. (Eds). Clinical Pharmacokinetics-Concepts and Applications (3rd ed.) (1995), Lea & Febiger, Philadelphia/London
Food and drugs administration, FDA Center for drug evaluation and research, Guidance for industry. Skin irritation and sensitization testing of generic transdermal drug products, December
W.L. Thompson, L.R. Brunelle, G.G. Enas, P.J. Simpson, L. Randy, Delta-limits mber 1999, From «Routine Laboratory Tests in Clinical Trials» Walker Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana in «Clinical Trials and Tribulations» 1988.
Standardisation of definitions and criteria of causality assessment of adverse drug reactions: drugs-induced liver disorders, International consensus Meeting Report, Int. J Clin. Pharmacol., Ther. Toxicol 28 (1990) 317-322.
Standardisation of definitions and criteria of causality assessment of adverse drug reactions: drugs-induced cytopenia, Int. J. Clin. Pharmacol., Ther. Toxicol. 29 (1991) 75-81.
Meikle A.W., Arver S., Dobs A.S., Sanders S.W., Rajaram L., and Mazer N.A. Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site-a clinical research center study. J. Clin. Endocrinol. Metab. 81 (1996) 1832-1840
Mazer N., Bell D., Wu J., Fischer J., Cosgrove M., and Eliers B. Comparison of the steady state pharmacokinetics, metabolism and variability of a transdermal testosterone patch versus a transdermal gel in hypogonadal men. J. Sex Med. 2 (2005) 213-226
In: Meikle A.W., Arver S., Dobs A., Sanders S., Mazer N., and Bhasin S. (Eds). Androderm: A Permeation Enhanced Non-scrotal Testosterone Transdermal System for the Treatment of Male Hypogonadism, Pharmacology, Biology and Clinical Application of Androgens (1996), Wiley-Liss Inc.
Wilson D.E., Kaidbay K., Boike S.C., and Jorkasky D.K. Use of topical corticosterol pre-treatment to reduce the incidence and severity of skin reactions associated with testosterone transdermal delivery. Clin. Ther. 20 (1998) 229-306
Yu Z., Gupta S.K., Hwang S.S., Cook D.M., Duckett M.J., and Atkinson L.E. Transdermal testosterone administration in hypogonadal men: comparison of pharmacokinetics at different sites of application and at the first and fifth days of application. J. Clin. Pharmacol. 37 (1997) 1129-1138
Yu Z., Gupta S.K., Hwang S.S., Kipnes M.S., Mooradian A.D., Snyder P.J., and Atkinson L.E. Testosterone pharmacokinetics after application of an investigational transdermal system in hypogonadal men. J. Clin. Pharmacol. 37 (1997) 1139-1145