Clinical pharmacology of recombinant human luteinizing hormone: Part II. Bioavailability of recombinant human luteinizing hormone assessed with an immunoassay and an in vitro bioassay.
OBJECTIVE
To assess the single-dose pharmacokinetics of a recombinant human LH preparation administered by the i.v., i.m., and s.c. route.


METHODS
Prospective, randomized cross-over study.


METHODS
Phase I clinical research environment.


METHODS
Twelve healthy pituitary down-regulated females.


METHODS
Subjects received single i.v., i.m., and s.c. doses of 10,000 IU of recombinant human LH, each separated by 1 week.


METHODS
Pharmacokinetic parameters.


RESULTS
After single i.v. administration, the pharmacokinetics were described by a two-compartment model, after i.m. or s.c. administration, by a one-compartment model with zero order absorption and a lag time. Using the immunoassay, after i.v. administration initial half-life was 1 hour and terminal half-life was 10 hours (half-life was prolonged after extravascular administration, suggesting rate-limiting absorption). Total serum clearance was 2.6 L/h, and steady, state volume of distribution was 14 L. Observed Cmax, after i.m. and s.c. administration, was 43 IU/L with median tmax of 9 hours (i.m.) and 5 hours (s.c.). Bioavailability was 0.54 (i.m.) and 0.56 (s.c.). The pharmacokinetics of LH are comparable using an in vitro bioassay.


CONCLUSIONS
The terminal half-life of recombinant human LH is around 12 hours and is slightly prolonged after extravascular administration. The pharmacokinetics are similar after i.m. and s.c. injection, and one-half the administered dose is available systemically.
le Cotonnec
J Y
JY
Ares-Serono International S.A., Geneva, Switzerland.
Porchet
H C
HC
Beltrami
V
V
Munafo
A
A
D000328:Adult; D000818:Animals; D001681:Biological Assay; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D017273:Goserelin / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007118:Immunoassay; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects; D011446:Prospective Studies; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone