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Evaluation of the Absolute Oral Bioavailability and Bioequivalence of Erlotinib, an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase, in a Randomized, Crossover Study in Healthy Subjects

From CV Therapeutics, Inc, Palo Alto, California (Dr Frohna); Genentech, Inc, South San Francisco, California (Dr Lu, Mr Eppler, Dr Ling, Dr Kenkare-Mitra, Dr Lum); OSI Pharmaceuticals, Inc, Boulder, Colorado (Dr Hamilton, Ms Wolf); and Hoffmann-La Roche Pharmaceuticals, Nutley, New Jersey (Dr Rakhit).

A randomized, open-label, 2-period crossover study was conducted to evaluate the bioequivalence of 6 tablets of erlotinib 25 mg and 1 tablet of erlotinib 150 mg (arm A, n = 42) and the oral bioavailability of the 150-mg tablet versus a 25-mg intravenous infusion (arm B, n = 20) in healthy subjects. The washout period was 2 weeks between treatments. Plasma concentrations of erlotinib and its active metabolite, OSI-420, were measured after each dose. The ratios of geometric means for AUC_0- and C_max of erlotinib following 6 tablets of erlotinib 25 mg and 1 tablet of erlotinib 150 mg were (1 and 0.95) within the predefined bioequivalence range of 0.80 to 1.25. The mean absolute oral bioavailability, using compartmental analysis, was estimated as 59% (95% confidence interval, 55%-63%). Overall, 6 tablets of erlotinib 25 mg are bioequivalent to a single 150-mg tablet. Both intravenous and oral erlotinib were generally well tolerated with an estimated bioavailability of 59% following oral administration.

Key Words: Erlotinib • bioequivalence • bioavailability

Address for reprints: Bert L. Lum, PharmD, Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech, Inc, 1 DNA Way (MS-70), Room 20207, South San Francisco, CA 94080.

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