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Erschienen in:
01.04.2005 | Short Communication
Bioavailability and pharmacokinetics of the investigational anticancer agent XK469 (NSC 698215) in rats following oral and intravenous administration
Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2005
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Purpose
To determine the oral bioavailability of R-XK469, a water-soluble investigational anticancer agent undergoing phase I clinical trials as an intravenous product.
Methods
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.
Results
The pharmacokinetic parameters of XK469 following oral and IV administrations, respectively, were (mean±SD): Cmax 138±64 and 404±355 μg/ml; AUC0–∞ 2381±773 and 2854±1924 μg h/ml; and elimination half-life (T1/2) 12.9±5.8 and 13.5±7.8 h Tmax was 2.92±1.92 h following oral dosing. Oral R-XK469 was 83% bioavailable.
Conclusion
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.