Systematic delivery of the luteinizing hormone-releasing hormone (LH-RH) antagonist cetrorelix (SB-75) via pulmonary instillation in the unanesthetized awake sheep

The pharmacokinetics of Cetrorelix acetate (SB-75), [Ac-D-Nal(2)¹, D-Phe(4Cl)², D-Pal(3)³, D-Cit⁶, D-Ala¹⁰]LH-RH, a highly potent LH-RH antagonist following i.v. injection and intratracheal instillation (i.t.), were determined in five unanesthetized, awakw sheep in a cross-over design. After i.t. administration the mean terminal t 1 2 was 11.6±5.2 h, similar to the i.v. elimination t 1 2 of 10.1±0.9 h. Mean residence time (MRT) was prolonged to 11.0±3.4 h vs. 5.9±1.3h i.v., and mean absorption time (MAT) was 5.6 ± 3.9 h. C_max of 134±79 ng/ml was reached after 1.8±0.5 h (tmax). The mean i.t. bioavailability was 15.4±10.6%.