Testosterone Release From a Subcutaneous, Biodegradable Microcapsule Formulation (Viatrel) in Hypogonadal Men

Abstract

Men with hypogonadism require testosterone replacement for optimal health. In the United States, testosterone is currently administered by daily transdermal patches, topical gels or intramuscular injections every 1-3 weeks. Biodegradable polylactideco-glycolide microcapsules are currently used for long-term drug delivery in humans. Such microcapsules that contain testosterone could provide a better means of long-term testosterone therapy. We therefore studied the pharmacokinetics and pharmacodynamics of testosterone release from testosterone microcapsules in men with hypogonadism. Fourteen men who had been treated previously with testosterone were enrolled in an open-label, prospective study of testosterone microcapsule administration. Subjects were enrolled if 2 consecutive serum total testosterone levels were lower than 8.7 nmol/L after a 4-week washout from testosterone therapy. Subjects were injected with a single dose of either 267 mg (n = 7) or 534 mg (n = 7) of (Viatrel) testosterone microcapsule, and serum total testosterone, dihydrotestosterone, estradiol, sex-hormone binding globulin, luteinizing hormone, and follicle-stimulating hormone levels were determined at days -14, -7, and O before the injection; at days 1, 2, and 7 after the injection; and then weekly thereafter for 8-12 weeks. Mean serum total testosterone levels peaked immedi-M en with hypogonadism requ ire testosterone replacement therapy to maintain normal bone and muscle mass, strength, and sexual function (Katznelson et al, 1996;Behre et al , 1997; Bhasin and Bremner, 1997;Snyder et al, 2000;Wang et al , 2000). In the United States, testosterone is administered by intramuscular injections, patches, or a recently approved transdermal gel. Each of these modes of testosterone delivery, however, have drawbacks. Injections, although inexpensive, must be given deeply into a large muscle every 1-3 weeks to maintain normal serum testosterone levels and are uncomfort- 84ately following injection on day 1 at 25.2 :!: 2.6 nmol/L in the 267 mg group and 34.7 :!: 2.4 nmol/L in the 534 mg group. Total serum testosterone levels declined gradually and fell below 8.7 nmol/L at 42 days after injection in the 267 mg group, and 70 days after injection in the 534 mg group. Estradiol and dihydrotestosterone levels followed a similar pattern. Mean serum free testosterone also peaked immediately following injection on day 1 at 0.51 :!: 0.05 nmol/L in the 267 mg group and 0.97 :!: 0.08 nmol/L in the 534 mg group. No significant adverse reactions were seen, although 2 subjects complained of transient tenderness and fullness at their injection sites. We conclude that a single injection of 534 mg of testosterone microcapsules to men with hypogonadism normalizes serum hormone levels for up to 10--11 weeks, albeit with a pronounced early peak and a relatively long period of low-normal serum total testosterone. Subcutaneously administered testosterone microcapsules may provide a safe and convenient method for the long-term treatment of male hypogonadism or ...

Serum Testosterone and Estradiol in Sudden Infant Death

“…Each specimen was placed in a sealed polypropylene tube labeled with the study number and stored frozen (<210°C) until submitted (without further identification) for analysis of total testosterone (etherextracted) and estradiol by highly specific time-resolved fluoroimmunoassay (Delfia; Wallac Oy, Turku, Finland). 26 The lower limits of detection for testosterone and estradiol were 0.5 nmol and 50 pmol, respectively. Mean intraassay and interassay coefficients of variation were 3.1% and 4.5% for testosterone and 2.4% and 3.8% for estradiol.…”

Effect of Environmental Enrichment on the Behavior and Welfare of Japanese Broilers at a Commercial Farm

“…Testosterone therapy is a popular treatment for male hypogonadism humans (Jockenhövel, 2004). For instance, Amory et al (2002) reported that mean serum testosterone levels (726 pg/ml) peaked immediately following an injection of 6. 3 mg/d of testosterone.…”

Testosterone replacement therapy for male hypogonadism: Part III. Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents

“…98,99 In a US study of hypogonadal men, the effects of T micro 267 mg were evaluated for up to 8 weeks and 534 mg for up to 12 weeks. 100 T micro resulted in rapid and prolonged restoration of T to eugonadal levels, with C avg values of 413-522 ng/dl and a halflife of 20.4-22.3 days 100 over the dose range. Serum T peaked at 731 ng/dl on day 2 after the lower dose and at 995 ng/dl on day 1 after the higher dose.…”

“…Serum T peaked at 731 ng/dl on day 2 after the lower dose and at 995 ng/dl on day 1 after the higher dose. 100 T micro significantly enhanced the quality and duration of erections, as well as relieving feelings of irritability from baseline. Treatment was well tolerated.…”