Journal of Clinical Endocrinology & Metabolism, Vol 80, 667-673, Copyright © 1995 by Endocrine Society

ARTICLES

Pharmacokinetics of recombinant human luteinizing hormone after intravenous, intramuscular, and subcutaneous administration in monkeys and comparison with intravenous administration of pituitary human luteinizing hormone

HC Porchet, JY Le Cotonnec, B Neuteboom, S Canali and G Zanolo
Istituto di Ricerche Biomediche Antoine Marxer, RBM S.p.A., Ivrea, Italy.

To assess the pharmacokinetics of recombinant human LH (rhLH) in monkeys, we measured serum LH levels after single iv injection and after single and repeated doses by the im or sc route. A single iv bolus of 400 IU/kg rhLH or pituitary hLH (phLH) in six cynomolgus monkeys resulted in parallel concentration-time curves. The initial and terminal half-lives of rhLH (0.8 and 11 h) were comparable to those of phLH (0.6 and 10 h). The serum levels of phLH were consistently higher due to the fact that the immunological dose of phLH was higher. Administration of increasing iv doses of rhLH (10, 63, and 400 IU/kg) to six monkeys showed that the pharmacokinetics are linear over this dose range. The total clearance for the two higher doses was 0.03 L/h.kg. Systemic bioavailability was 50% after a single sc injection of 400 IU/kg and 61% after a single im injection of the same dose. The peak concentration (180 IU/L) after im injection was reached after 2.7 h. This was higher and sooner than after sc injection (110 IU/L after 5.3 h). The terminal half-life by both routes was similar to that seen after iv injection (11 h). Daily sc or im administration of 63 IU/kg for 7 days confirmed these findings. There was no accumulation of rhLH. Some monkeys developed antibodies, especially after repeated administration. They were excluded from the analysis. No significant local or systemic adverse events occurred.

This article has been cited by other articles:

				B. C. Fauser, D. de Jong, F. Olivennes, H. Wramsby, C. Tay, J. Itskovitz-Eldor, and H. G. van Hooren Endocrine Profiles after Triggering of Final Oocyte Maturation with GnRH Agonist after Cotreatment with the GnRH Antagonist Ganirelix during Ovarian Hyperstimulation for in Vitro Fertilization J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 709 - 715. [Abstract] [Full Text] [PDF]

				The European Recombinant LH Study Group Human Recombinant Luteinizing Hormone Is as Effective as, But Safer Than, Urinary Human Chorionic Gonadotropin in Inducing Final Follicular Maturation and Ovulation in in Vitro Fertilization Procedures: Results of a Multicenter Double-Blind Study J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2607 - 2618. [Abstract] [Full Text] [PDF]

				E.S. Sills, D. P. Levy, M. Moomjy, M. McGee, and Z. Rosenwaks A prospective, randomized comparison of ovulation induction using highly purified follicle-stimulating hormone alone and with recombinant human luteinizing hormone in in-vitro fertilization Hum. Reprod., September 1, 1999; 14(9): 2230 - 2235. [Abstract] [Full Text] [PDF]

				T. E. R. H. L. S. Group Recombinant Human Luteinizing Hormone (LH) to Support Recombinant Human Follicle-Stimulating Hormone (FSH)-Induced Follicular Development in LH- and FSH-Deficient Anovulatory Women: A Dose-Finding Study J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1507 - 1514. [Abstract] [Full Text]

				B. C. J. M. Fauser and A. M. van Heusden Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences Endocr. Rev., February 1, 1997; 18(1): 71 - 106. [Abstract] [Full Text]