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Pharmacokinetic and pharmacodynamic interactions between recombinant human luteinizing hormone and recombinant human
J Y le Cotonnec1, E Loumaye, H C Porchet
1Serono International S.A., Geneva, Switzerland.
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 s.c. 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.