Bioavailability of sorafenib tablets administered as a liquid suspension.

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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
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
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 (Cmax) and time to Cmax (Tmax) were assessed by noncompartmental analysis.
Geometric mean (percentage coefficient of variation) or median results
for these pharmacokinetic assessments are shown in the table.
The pharmacokinetics of sorafenib, when administered as a liquid
suspension of tablets in water, were similar to the pharmacokinetics of
tablets swallowed whole.