CLINICAL-PHARMACOLOGY OF RECOMBINANT HUMAN LUTEINIZING-HORMONE - PARTII - BIOAVAILABILITY OF RECOMBINANT HUMAN LUTEINIZING-HORMONE ASSESSED WITH AN IMMUNOASSAY AND AN IN-VITRO BIOASSAY

Objective: To assess the single-dose pharmacokinetics of a recombinant human LH preparation administered by the IV, IM, and SC route. Design : Prospective, randomized cross-over study. Setting: Phase I clinical research environment. Patient(s): Twelve healthy pituitary down-regula ted females. Intervention(s): Subjects received single IV, IM, and SC doses of 10,000 IU of recombinant human LH, each separated by 1 week. Main Outcome Measure(s): Pharmacokinetic parameters. Result(s): After single IV administration, the pharmacokinetics were described by a two -compartment model, after IM or SC administration, by a one-compartmen t model with zero order absorption and a lag time. Using the immunoass ay, after IV administration initial half-life was 1 hour and terminal half-life was 10 hours (half-life was prolonged after extravascular ad ministration, suggesting rate-limiting absorption). Total serum cleara nce was 2.6 Lih, and steady-state volume of distribution was 14 L. Obs erved C-max, after IM and SC administration, was 43 IU/L with median t (max) of 9 hours (IM) and 5 hours (SC). Bioavailability was 0.54 (IM) and 0.56 (SC). The pharmacokinetics of LH are comparable using an in v itro bioassay. Conclusion(s): The terminal half-life of recombinant hu man LH is around 12 hours and is slightly prolonged after extravascula r administration. The pharmacokinetics are similar after IM and SC inj ection, and one-half the administered dose is available systemically. (C) 1998 by American Society for Reproducive Medicine.