Bioavailability and pharmacokinetics of the investigational anticancer agent XK469 (NSC 698215) in rats following oral and intravenous administration
| Autor: | Sen-Lin Zhou, Ramesh R. Boinpally, Patricia LoRusso, Ralph E. Parchment |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Pharmacology Cancer Research business.industry Pharmacology toxicology Administration Oral Biological Availability Antineoplastic Agents Toxicology Rats Bioavailability Rats Sprague-Dawley Clinical trial Oncology Pharmacokinetics Oral administration Quinoxalines Injections Intravenous Animals Medicine Pharmacology (medical) business Half-Life |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 55:404-407 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-004-0862-6 |
| Popis: | To determine the oral bioavailability of R-XK469, a water-soluble investigational anticancer agent undergoing phase I clinical trials as an intravenous product.R-XK469 was administered to two groups of catheterized Sprague-Dawley rats via the oral and IV routes at a dose of 10 mg/kg and blood samples were collected at predetermined times. XK469 in plasma samples was quantified using a HPLC method. The pharmacokinetic parameters were computed using WinNonlin 4.0.1 software.The pharmacokinetic parameters of XK469 following oral and IV administrations, respectively, were (mean+/-SD): C(max) 138+/-64 and 404 +/- 355 microg/ml; AUC(0-infinity) 2381 +/- 773 and 2854 +/- 1924 microg h/ml; and elimination half-life (T(1/2)) 12.9 +/- 5.8 and 13.5 +/- 7.8 h T(max) was 2.92+/-1.92 h following oral dosing. Oral R-XK469 was 83% bioavailable.Together with the antitumor efficacy of oral XK469 shown in preclinical models and its schedule dependency, these results indicate the promise of developing an oral dosage form of R-XK469 for clinical development. |
| Databáze: | OpenAIRE |
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