Clinical pharmacology of recombinant human luteinizing hormone: Part I. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone

Objective: To assess the pharmacokinetics after IV administration of a recombinant human LH and to compare them to those of a reference hMG preparation containing urinary human LH. Design: Prospective, dose-escalating, cross-over study. Setting: Phase I clinical research environment. Patient(s): Twelve healthy pituitary down-regulated females. Intervention(s): Subjects received single TV doses of 300, 10,000, and 40,000 IU of recombinant human LH, followed by a single IV dose of 300 IU of hMG, all separated by 1 week. Main Outcome Measure(s): Pharmacokinetic parameters. Results: For both preparations, LH serum levels were well described by similar biexponential models. The pharmacokinetics of recombinant human LH were linear over the 300 to 40,000 IU range. After a rapid distribution phase with an initial half-life of 1 hour, both recombinant human LH and urinary human LH were eliminated with a terminal half-life of 10-12 hours. Total serum clearance was 1.7 L/h with <4% and 30% of the dose being eliminated in the urine for recombinant human LH and urinary human LH, respectively. The volume of distribution at steady-state was approximately 10 L. Irrespective of the dose, recombinant human LH was well tolerated. Conclusion(s): The pharmacokinetics of recombinant human LH are linear with dose and similar to those of urinary human LH. (C) 1998 by American Society for Reproductive Medicine.