Callies F, Kollenkirchen U, von zur Mühlen C, Tomaszewski M, Beer S, Allolio B
Department of Endocrinology, Medical University Hospital Wuerzburg, Wuerzburg, Germany.
Exp Clin Endocrinol Diabetes. 2003 Jun;111(4):203-8. doi: 10.1055/s-2003-40464.
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.
在实验动物中，睾酮（T）治疗的一个主要障碍是在外源性给予T后，难以维持长期生理/合成代谢稳定的血清水平。在两项互补研究中，我们调查了不同T制剂在雄性大鼠中的药代动力学特性。研究I. 成熟雄性Wistar大鼠（> 380 g，每组n = 4 - 7）分为四个治疗组：（1）假手术未去势（非ORX）并给予安慰剂；（2）去势（ORX）并皮下植入睾酮丸剂（TP）（15、25、75 mg/60天释放或安慰剂丸剂）；（3）ORX并单次注射十一酸睾酮（TUD）（31、62.5或125 mg/kg体重皮下注射（s.c.）或赋形剂；（4）ORX并丙酸睾酮（Tprop）（10、20、40 mg/月）或赋形剂单次皮下注射。在基线和4周内每周测量血清T。研究II. 成熟雄性Wistar大鼠（180 - 200 g）随机分配到5个实验组之一（每组n = 5 - 6）：（1）正常未治疗大鼠（对照组）；（2）ORX未治疗大鼠，以及接受三种治疗方案之一的非ORX大鼠；（3）250 mg/kg体重TUD肌肉注射（TUD 250）；（4）500 mg/kg体重TUD肌肉注射（TUD 500）；（5）100 - mg睾酮丸剂/90天释放皮下注射（TP 100）。在给予T后，在基线和6周内定期测量血清T。在两项研究中，TUD的动力学曲线显示在数周内具有良好的持续稳态水平。相比之下，皮下丸剂释放的睾酮导致血清T水平升高的持续时间短于预期，且个体间变异性高。给予Tprop仅导致血清T短暂升高，注射后14天血清T水平就已降低。总之，单次注射TUD（100 mg/kg体重皮下注射）可有效诱导ORX大鼠的生理睾酮水平至少持续四周。单次注射高剂量TUD（500 mg/kg体重肌肉注射）可使非ORX大鼠的合成代谢睾酮浓度超生理水平长达六周。TUD优于其他T释放制剂，是实验动物中给予T的一种方便有效的工具。
