Bioavailability of sorafenib tablets administered as a liquid suspension.

Author(s): J. T. Lettieri, R. Dubowy, C. Xia, C. Rotolo, M. A. Zinny; Bayer HealthCare Pharmaceuticals, Montville, NJ; ProMedica Clinical Research Center, Inc., Boston, MA

Abstract:

Background: Sorafenib is a multikinase inhibitor currently approved by the FDA for the treatment of advanced renal-cell carcinoma (RCC) and unresectable hepatocellular carcinoma (HCC), and by the EMEA for the treatment of HCC and advanced RCC. Sorafenib is available as a tablet formulation. Some patients who are unable to swallow tablets have suspended sorafenib tablets in a liquid for ease of administration. We performed a study to assess whether this process alters the bioavailability of sorafenib.

Methods: Twenty-six healthy male volunteers were enrolled. Utilizing a randomized, crossover design, subjects received either two 200-mg intact tablets (IT) with 8 ounces water, or two 200-mg tablets disintegrated over 10 minutes in 2 ounces of water (ST), with an additional 6 ounces of water swallowed as a rinse of the dosing vessel. Doses were separated by a 10- to 14-day washout period. Following each dose, blood samples were collected at designated times up to 144 hours after dosing for measurement of sorafenib plasma concentrations. Sorafenib was assayed by a validated liquid chromatography/mass spectrometry method. The pharmacokinetic parameters area under the curve (AUC), maximum concentration (C_max) and time to C_max (T_max) were assessed by noncompartmental analysis.

Results: Geometric mean (percentage coefficient of variation) or median results for these pharmacokinetic assessments are shown in the table.

Conclusions: The pharmacokinetics of sorafenib, when administered as a liquid suspension of tablets in water, were similar to the pharmacokinetics of tablets swallowed whole.