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

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 (100 mu g) of C-14-drug was administered orally (period 1) and intravenously by 30 min infusion (period 2). In period 3 an intravenous tracer dose (100 mu g) of C-14-drug was administered simultaneously with an oral unlabelled therapeutic dose (120 mg). Plasma was collected from all 3 periods and analysed for both total C-14 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 C-14. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13 L/h, CLR 4.1 L/h, V-ss 54L, t(1/2) 16h; therapeutic close: CL 16 L/h, CLR 6.2 L/h, V-ss, 64 L, 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 close for this transporter dependent compound. (C) 2010 Elsevier B.V. All rights reserved.