Pharmacokinetics and Pharmacodynamics of a Novel Depot Formulation of Abarelix, a Gonadotropin-Releasing Hormone (GnRH) Antagonist, in Healthy Men Ages 50 to 75

This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel depot formulation of abarelix, a new gonadotropin‐releasing hormone (GnRH) antagonist. This was an open‐label, sequential two‐phase study in healthy male subjects ages 50 to 75. Subjects received a single intramuscular (IM) dose of 15 μg/kg abarelix injectable solution, followed by a 21‐day washout period and a subsequent intramuscular dose of 100 mg abarelix depot. The PK and the hormonal suppression effects of abarelix were evaluated based on testosterone (T), dihydrotestosterone (DHT), follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) levels. Abarelix provides immediate competitive blocking of the GnRH receptors on pituitary gonadotropes without causing release of gonadotropins, and these effects are reversible. The mean IC50s of abarelix for T, DHT, FSH, and LH were 2.08, 3.42, 6.43, 4.25 ng/mL, respectively. The mean relative bioavailability of the depot formulation in reference to the injectable solution was 0.52. The mean tmax and terminal t1/2 for abarelix after administration of abarelix injectable solution and abarelix depot injection were 1 hour and 3 days and 0.22 days (5.3 h) and 13.2 days, respectively. The novel abarelix depot formulation used in this study significantly improved the duration of abarelix delivery and pharmacological activities compared to the injectable formulation, without causing any safety issues.