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Pharmacokinetics and Pharmacodynamics of a Novel Depot Formulation of Abarelix, a Gonadotropin‐Releasing Hormone (GnRH) Antagonist, in Healthy Men Ages 50 to 75
Author(s) -
Wong Shekman L.,
Lau David T.W.,
Baughman Sharon A.,
Fotheringham Nick,
Menchaca Dora,
Garnick Marc B.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004264920
Subject(s) - depot , luteinizing hormone , pharmacodynamics , pharmacokinetics , medicine , testosterone (patch) , endocrinology , gonadotropin releasing hormone antagonist , follicle stimulating hormone , gonadotropin releasing hormone , hormone , gonadotropin , bioavailability , dihydrotestosterone , hormone antagonist , pharmacology , androgen , endocrine system , archaeology , history
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 IC 50 s 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 t max and terminal t 1/2 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.