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
 
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 (Cmax) and time to Cmax (Tmax) 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.