Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability

Lappin, Graham, Shishikura, Yoko, Jochemsen, Roeline , Weaver, Richard John, Gesson, Charlotte, Houston, Brian, Oosterhuis, Berend, Bjerrum, Ole J., Rowland, Malcolm and Garner, Colin (2010) Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability. European Journal of Pharmaceutical Sciences, 40 (2). pp. 125-131. ISSN 0928-0987

Full content URL: http://dx.doi.org/10.1016/j.ejps.2010.03.009

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Abstract

A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100μg) of 14C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100μg) of 14C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total 14C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine was collected and analysed for total 14C. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13L/h, CL R 4.1L/h, V ss 54L, t 1/2 16h; therapeutic dose: CL 16L/h, CL R 6.2L/h, V ss 64L, t 1/2 12h. The absolute oral bioavailability of fexofenadine was 0.35 (microdose 0.41, therapeutic dose 0.30). Despite a 1200-fold difference in dose of fexofenadine, the microdose predicted well the pharmacokinetic parameters following a therapeutic dose for this transporter dependent compound. © 2010 Elsevier B.V.

Keywords:Absolute oral bioavailability, AMS fexofenadine, Accelerator mass spectrometry, Microdosing
Subjects:B Subjects allied to Medicine > B230 Pharmacy
Divisions:College of Science > School of Pharmacy
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ID Code:7350
Deposited On:27 Feb 2013 16:43

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