Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Pharmaceutical Sciences |
| Vol/bind | 40 |
| Udgave nummer | 2 |
| Sider (fra-til) | 125-31 |
| Antal sider | 6 |
| ISSN | 0928-0987 |
| DOI | |
| Status | Udgivet - 2010 |
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I: European Journal of Pharmaceutical Sciences, Bind 40, Nr. 2, 2010, s. 125-31.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Pharmacokinetics of fexofenadine
T2 - evaluation of a microdose and assessment of absolute oral bioavailability
AU - Lappin, Graham
AU - Shishikura, Yoko
AU - Jochemsen, Roeline
AU - Weaver, Richard John
AU - Gesson, Charlotte
AU - Houston, Brian
AU - Oosterhuis, Berend
AU - Bjerrum, Ole Jannik
AU - Rowland, Malcolm
AU - Garner, Colin
PY - 2010
Y1 - 2010
N2 - 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 (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C 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 (14)C. 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.
AB - 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 (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C 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 (14)C. 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.
U2 - 10.1016/j.ejps.2010.03.009
DO - 10.1016/j.ejps.2010.03.009
M3 - Journal article
C2 - 20307657
SN - 0928-0987
VL - 40
SP - 125
EP - 131
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 2
ER -