Leuprolide
Leuprolide, a peptide. Nonapeptide GnRH analog — D-Leu⁶ + Pro⁹-NEt modifications resist degradation, raise receptor affinity ~15× over… Subcutaneous half-life 3.6 h.
Nonapeptide GnRH analog — D-Leu⁶ + Pro⁹-NEt modifications resist degradation, raise receptor affinity ~15× over native GnRH. Initial pulsatile spike flares LH/FSH → testosterone / oestrogen surge in first week (testosterone-flare in prostate cancer); continuous chronic exposure desensitises and down-regulates pituitary GnRH-R → castrate gonadal steroid levels within ~3–4 weeks. Depot microspheres / in-situ-forming gel formulations release drug over 1, 3, 4, or 6 months.
PK describes IMMEDIATE-RELEASE leuprolide, not a depot. Sennello 1986 (PMID:3083092), 6 healthy men, 1 mg SC and IV crossover, verbatim "The mean beta half-life after the intravenous dosings was 2.9 h and after the subcutaneous dosings was 3.6 h" and "The mean volume of distribution at steady state from the intravenous and subcutaneous doses were 26.5 and 37.1 L, respectively". F 0.94 from Adjei 1992 (PMID:1553349), healthy men, verbatim "The s.c. injection was 94% bioavailable compared with i.v." The previous citation (PMID:12083977) is a review of DEPOT leuprorelin whose own numbers are 3.6 h and 37 L for immediate-release and 27 L for the 15 mg depot — the stored 28 L sat between the two formulations. ka 0.05 /h dropped: it implies a 14 h absorption half-life, which is neither immediate-release nor depot.
Pharmacokinetics
- Subcutaneous — t½ 3.6 h · F 94% · Vd 37.1 L
Sources: PMID:12083977, PMID:3083092, PMID:1553349