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

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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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