AR. It has an affinity (Kd) of 0.25 to 0.5 nM for the human AR, which is about 2- to 3-fold higher than that of testosterone (Kd = 0.4 to 1.0 nM) and the dissociation rate of androstanolone from the AR is also about 5-fold slower than that of testosterone. The EC50 of androstanolone for activation of the AR is 0.13 nM, which is about 5-fold stronger than that of testosterone (EC50 = 0.66 nM). In bioassays, androstanolone has been found to be 2.5- to 10-fold more potent than testosterone. Upon intramuscular injection in rats, androstanolone is about 1.5- to 2.5-fold the potency of testosterone. Unlike testosterone and various other AAS, androstanolone cannot be aromatized, and for this reason, poses no risk of estrogenic side effects like gynecomastia at any dosage. In addition, androstanolone cannot be metabolized by 5α-reductase (as it is already 5α-reduced), and for this reason, is not potentiated in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland, thereby improving its ratio of anabolic to androgenic effects. However, androstanolone is nonetheless described as a very poor anabolic agent. This is attributed to its high affinity as a substrate for 3α-hydroxysteroid dehydrogenase (3α-HSD), which is highly expressed in skeletal muscle and inactivates androstanolone into 3α-androstanediol, a metabolite with very weak AR activity. Unlike androstanolone, testosterone is very resistant to metabolism by 3α-HSD, and so is not similarly inactivated in skeletal muscle. For the preceding reasons, androstanolone has been described as a "partial androgen". Pharmacokinetics Absorption The bioavailability of androstanolone differs considerably depending on its route of administration. Its oral bioavailability is very low, and androstanolone has been considered to be ineffective by the oral route. However, it has been used orally, and is described as a weak AAS by this route. The transdermal bioavailability of androstanolone is approximately 10%. Its bioavailability with intramuscular injection, on the other hand, is complete (100%). Doses of topical androstanolone gel of 16, 32, and 64 mg have been found to produce total testosterone and DHT levels in the low, mid, and high normal adult male range, respectively. Distribution The plasma protein binding of androstanolone is about 98.5 to 99.0%. It is bound 50 to 80% to sex hormone-binding globulin, 20 to 40% to albumin, and less than 0.5% to corticosteroid-binding globulin, with about 1.0 to 1.5% circulating freely or unbound. Metabolism The terminal half-life of androstanolone in the circulation (53