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.

DESIGN

Prospective, randomized cross-over study.

SETTING

Phase I clinical research environment.

PATIENT(S): Twelve healthy pituitary down-regulated females.

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

MAIN OUTCOME MEASURE(S): Pharmacokinetic parameters.

RESULT(S): 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.

CONCLUSION(S): 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.