Objective: To assess the pharmacokinetics of a recombinant human LH preparation and its pharmacokinetic and pharmacodynamic interactions with recombinant human follicle-stimulating hormone (FSH). Design: Prospective, randomized cross-over study. Setting: Phase I clinical research environment. Patient(s): Twelve healthy pituitary down-regulated females. Intervention(s): Subjects received 150 IU of SC recombinant human LH and FSH, either alone or in combination, followed by recombinant human LH and FSH once daily for 7 days. Main Outcome Measure(s): Pharmacokinetic parameters, ovarian follicle development. Result(s): No pharmacokinetic interaction between recombinant human LH and FSH was observed, with no significant difference in baseline-corrected maximal observed concentration over baseline, area under the concentration-time curve from t = 0 to t = 24 hours, or time to maximal concentration after single doses alone or in combination. After daily administration, the mean accumulation ratio was 1.6 for LH and 2.9 for; FSH, with absorption and terminal phase half-life estimates of 4 and 11 hours for LH and 8 and 16 hours for FSH, respectively. Combined administration of FSH and LH for 7 days was effective in stimulating ovarian follicular development and steroidogenesis, with large interindividual variability related to ovarian sensitivity. Conclusion(s): A new recombinant human LH preparation has a low accumulation ratio at steady-state and no pharmacokinetic or pharmacodynamic interactions with recombinant human FSH. (C) 1998 by American Society for Reproductive Medicine.
