Human pharmacokinetic and pharmacodynamic profiles of leuprorelin acetate depot in prostatic cancer patients

J Int Med Res. 1990:18 Suppl 1:42-56. doi: 10.1177/03000605900180S108.

Abstract

A total of 21 patients with advanced prostatic cancer and one patient with benign prostatic hypertrophy received 3.75, 7.5 or 15 mg leuprorelin acetate depot subcutaneously. Serum leuprorelin concentrations increased immediately after injection, reaching a peak concentration (range 13.1-54.5 ng/ml), which was directly proportional to dose, within 3 h. Mean drug levels subsequently declined to a plateau directly proportional to dose at 5 weeks. There was also a significant (P less than 0.01) dose-dependent increase in the area under the concentration-time curve for 0-35 days. Serum concentrations of luteinizing hormone and follicle stimulating hormone rose initially with all doses, followed by a rise in serum testosterone and dihydrotestosterone concentrations, which then fell sharply, within 3 weeks. A reduced level of follicle stimulating hormone subsequently occurred in all 20 evaluable patients and was maintained in 17 patients over 5 weeks. There was also marked initial suppression of luteinizing hormone levels in 15 patients and in 13 this continued. Castration levels of testosterone and dihydrotestosterone were maintained in all patients for up to 5 weeks. In two patients there was a complete response, in 14 a partial response and in three stable disease, with no significant differences in relation to dose. Clinical improvement and serum hormonal changes suggest that leuprorelin acetate depot is effective at a dose as low as 3.75 mg when given once every 4 weeks.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / blood
  • Gonadotropin-Releasing Hormone / pharmacokinetics
  • Gonadotropin-Releasing Hormone / pharmacology
  • Humans
  • Leuprolide
  • Luteinizing Hormone / blood
  • Male
  • Middle Aged
  • Prostatic Neoplasms / metabolism*
  • Randomized Controlled Trials as Topic

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Leuprolide