Abstract：
: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 microg/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.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Wong SL,Lau DT,Baughman SA,Fotheringham N,Menchaca D,Garnick MBdoi
10.1177/0091270004264920subject
Has Abstractpub_date
2004-05-01 00:00:00pages
495-502issue
5eissn
0091-2700issn
1552-4604pii
44/5/495journal_volume
44pub_type
临床试验,杂志文章abstract：:The confluence of rapid scientific advancements especially in protein engineering and recombinant technology, unmet medical needs, and commercial incentives have led to the development of the next generation of therapeutic proteins. Bispecific antibody constructs are one of the novel strategies that is being pursued, ...
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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