Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers

Abstract

The pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin (rHCG) were investigated in three studies of healthy volunteers. After single intravenous doses of 25, 250 and 1000 μg, rHCG and urinary HCG (uHCG) showed linear pharmacokinetics described by a bi-exponential model, although the area under the curve (AUC) for uHCG was ∼29% lower than for rHCG. After intramuscular or subcutaneous administration (absolute bioavailability, 40–50% for both), rHCG pharmacokinetics could be described by a first-order absorption, one-compartment model. During multiple subcutaneous dosing, the amount of HCG increased by ∼1.7-fold. A comparison of liquid and freeze-dried rHCG and freeze-dried uHCG showed pharmacokinetic bioequivalence. In down-regulated male subjects, single doses of 125 μg rHCG, given intravenously, intramuscularly or subcutaneously, produced comparable increases in serum testosterone, inhibin and 17β-oestradiol, with little further increase during repeated subcutaneous administration (in female subjects, this produced a sustained comparable increase in serum androstenedione and testosterone concentrations). In conclusion, the pharmacokinetics and pharmacodynamics of rHCG are similar to those of uHCG and are not affected by the use of different formulations. In healthy subjects, rHCG produces pharmacodynamic responses consistent with HCG physiology and is suitable for use in the same clinical indications as uHCG. The secured source and high purity of rHCG may offer important advantages.