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 i.v. 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 i.v. doses of 300, 10,000, and 40,000 IU of recombinant human LH, followed by a single i.v. 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.