Testosterone Undecanoate: A Useful Tool for Testosterone Administration in Rats

Abstract

A major obstacle of testosterone (T) treatment in experimental animals is the difficulty of maintaining long-term physiologic/anabolic steady serum levels after exogenous T administration. In two complementary studies we investigated the pharmacokinetic properties of different T formulations in male rats.

Study I

Mature male Wistar rats (> 380 g, n = 4 - 7/group) were divided into four treatment groups: 1) sham-operated non orchiectomised (non-ORX) and placebo; 2) orchiectomised (ORX) and subcutaneous testosterone pellets (TP) (15, 25, 75 mg/60 days release or placebo pellets); 3) ORX and a single injection of testosterone undecanoate (TUD) (31, 62.5 or 125 mg/kg body weight subcutaneously (s.c.) or vehicle; 4) ORX and testosterone propionate (Tprop) (10, 20, 40 mg/month) or vehicle as a single injection s.c. Serum T was measured at baseline and in weekly intervals for 4 weeks.

Study II

Mature male Wistar rats (180 - 200 g) were randomly assigned to one of 5 experimental groups (n = 5 - 6/group): 1) normal untreated rats (controls); 2) ORX untreated rats, and non-ORX rats receiving one of three treatment options; 3) 250 mg/kg body weight TUD i.m. (TUD 250); 4) 500 mg/kg body weight TUD i.m. (TUD 500); 5) 100-mg testosterone pellet/90 days release s.c. (TP 100). Serum T was measured at baseline and in intervals for 6 weeks after T administration.

In both studies, the kinetic profile of TUD showed favourable continuous steady state levels over several weeks. In contrast, testosterone release by subcutaneous pellets resulted in a shorter than expected duration of elevated serum T levels with high inter-individual variability. Tprop administration led to only a short-lasting serum T increase with low serum T levels already 14 days after injection.

In conclusion, a single injection of TUD (100 mg/kg body weight s.c.) is effective in inducing physiological testosterone levels in ORX rats for a minimum of four weeks. High dose TUD (500 mg/kg body weight i.m.) given as a single injection results in supraphysiological anabolic testosterone concentrations for up to six weeks in non-ORX rats. TUD was superior to other T release preparations and represents a convenient and effective tool for T administration in experimental animals.

Key words

Testosterone - testosterone undecanoate - pellets - pharmacokinetic - testosterone propionate

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