Oral administration of the GnRH antagonist acyline, in a GIPET®-enhanced tablet form, acutely suppresses serum testosterone in normal men: single-dose pharmacokinetics and pharmacodynamics
| Autor: | William J. Bremner, Edel O'toole, Michael J. McKenna, Thomas W. Leonard, John K. Amory, Stephanie T. Page |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Time Factors medicine.drug_class Administration Oral Biological Availability Gonadotropin-releasing hormone Toxicology Article Gonadotropin-Releasing Hormone Young Adult Follicle-stimulating hormone Pharmacokinetics Oral administration Internal medicine medicine Humans Testosterone Pharmacology (medical) Pharmacology Dose-Response Relationship Drug business.industry Fatty Acids Prostatic Neoplasms Luteinizing Hormone Androgen Endocrinology Oncology Pharmacodynamics Follicle Stimulating Hormone business Luteinizing hormone Oligopeptides Tablets |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 64:641-645 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-009-1038-1 |
| Popis: | GnRH analogs are useful for the treatment of prostate cancer, but require parenteral administration. The peptide GnRH antagonist acyline potently suppresses luteinizing hormone (LH) and testosterone in man; however, its clinical utility is limited by the requirement for frequent injections. The use of a proprietary enhancer system called GIPET®, which is based on medium-chain fatty acids, facilitates the oral bioavailability of peptides. We hypothesized that GIPET® enhancement would allow for the safe oral dosing of acyline for the treatment of prostate cancer. We enrolled eight healthy young men in a pharmacokinetic and pharmacodynamic study of 10, 20 and 40 mg doses of GIPET®-enhanced oral acyline. Blood for measurement of serum LH, FSH, testosterone and acyline was obtained prior to each dose of GIPET®-enhanced oral acyline and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 h after dosing. Serum LH, FSH and serum testosterone were significantly suppressed by all doses of GIPET®-enhanced oral acyline after 6 h, with suppression reaching a nadir 12 h after dosing. In addition, the 20 and 40 mg doses demonstrated sustained suppression of testosterone for 12–24 h. All hormone concentrations returned to normal 48 h after administration. There were no treatment-related serious adverse events, and laboratory assessments, including liver function tests and creatinine, were unaffected by treatment. Oral administration of GIPET®-enhanced acyline significantly suppresses testosterone and gonadotropins in normal men without untoward side effects and might have utility in the management of prostate cancer. |
| Databáze: | OpenAIRE |
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