Clinical pharmacology of recombinant human luteinizing hormone: Part II. Bioavailability of recombinant human luteinizing hormone assessed with an immunoassay and an in vitro bioassay

Abstract

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-regulated 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-compartment model with zero order absorption and a lag time. Using the immunoassay, after IV administration initial half-life was 1 hour and terminal half-life was 10 hours (half-life was prolonged after extravascular administration, suggesting rate-limiting absorption). Total serum clearance was 2.6 L/h, and steady-state volume of distribution was 14 L. Observed 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 vitro bioassay. Conclusion(s): The terminal half-life of recombinant human LH is around 12 hours and is slightly prolonged after extravascular administration. The pharmacokinetics are similar after IM and SC injection, and one-half the administered dose is available systemically.