Pharmacokinetic profile of recombinant human (rh) inhibin A and activin A in the immature rat. I. Serum profile of rh-inhibin A and rh-activin A in the immature female rat

The serum pharmacokinetics of recombinant human inhibin A (rh-inhibin A) and rh-activin A were examined in immature female Sprague Dawley-derived rats after iv and sc injection of the drugs. After iv administration of rh-inhibin A (120 μg/kg), the serum concentrations were described by a biexponential equation. The weight-normalized clearance was 21.3 ml/min·kg, and the initial (t_1/α) and terminal (t_{1/ 2β}) half-lives were 2.9 min and 37.9 min, respectively. Subcutaneous administration of 120 μg/kg rh-inhibin A resulted in a peak serum concentration of 10.6 ng/ml at 30.8 min after injection. Approximately 24% of the sc administered material was absorbed. Serum concentrations of rh-activin A also declined biexponentially after iv injection of the drug (120 μg/kg). The clearance of rh-activin A was 5.1 ml/min· kg, the t_1/2α was 6.1 min, and the t_1/2β was 46.3 min. The peak serum concentration of rh-activin A (104.7 ng/ml) was achieved 24.7 min after sc delivery of the drug. The bioavailability of the sc dose was 38%. Iodinated rh-inhibin A and rh-activin A were used to examine the serum forms and metabolites of the drugs. [¹²⁵I]rh-inhibin A and [¹²⁵I] rh-activin A associated with two serum-binding proteins. Within 2 min of iv injection, the labeled hormones bound follistatin and α-2-macroglobulin. Even though rh-inhibin A and rh-activin A are structurally similar and appear to bind to the same serum proteins, their disposition in the immature rat differ.