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.
OBJECTIVE: To assess the pharmacokinetics after i.v. administration of a recombinant humanLH and to compare them to those of a reference hMG preparation containing urinary humanLH. 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 humanLH, 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 humanLH 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 humanLH and urinary humanLH 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 humanLH and urinary humanLH, respectively. The volume of distribution at steady-state was approximately 10 L. Irrespective of the dose, recombinant humanLH was well tolerated. CONCLUSION(S): The pharmacokinetics of recombinant humanLH are linear with dose and similar to those of urinary humanLH.