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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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 Jannik; Rowland, Malcolm; Garner, Colin.

In: European Journal of Pharmaceutical Sciences, Vol. 40, No. 2, 2010, p. 125-31.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lappin, G, Shishikura, Y, Jochemsen, R, Weaver, RJ, Gesson, C, Houston, B, Oosterhuis, B, Bjerrum, OJ, Rowland, M & Garner, C 2010, 'Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability', European Journal of Pharmaceutical Sciences, vol. 40, no. 2, pp. 125-31. https://doi.org/10.1016/j.ejps.2010.03.009

APA

Lappin, G., Shishikura, Y., Jochemsen, R., Weaver, R. J., Gesson, C., Houston, B., Oosterhuis, B., Bjerrum, O. J., Rowland, M., & Garner, C. (2010). Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability. European Journal of Pharmaceutical Sciences, 40(2), 125-31. https://doi.org/10.1016/j.ejps.2010.03.009

Vancouver

Lappin G, Shishikura Y, Jochemsen R, Weaver RJ, Gesson C, Houston B et al. Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability. European Journal of Pharmaceutical Sciences. 2010;40(2):125-31. https://doi.org/10.1016/j.ejps.2010.03.009

Author

Lappin, Graham ; Shishikura, Yoko ; Jochemsen, Roeline ; Weaver, Richard John ; Gesson, Charlotte ; Houston, Brian ; Oosterhuis, Berend ; Bjerrum, Ole Jannik ; Rowland, Malcolm ; Garner, Colin. / Pharmacokinetics of fexofenadine : evaluation of a microdose and assessment of absolute oral bioavailability. In: European Journal of Pharmaceutical Sciences. 2010 ; Vol. 40, No. 2. pp. 125-31.

Bibtex

@article{447d4a007d0e11df928f000ea68e967b,
title = "Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability",
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 (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.",
author = "Graham Lappin and Yoko Shishikura and Roeline Jochemsen and Weaver, {Richard John} and Charlotte Gesson and Brian Houston and Berend Oosterhuis and Bjerrum, {Ole Jannik} and Malcolm Rowland and Colin Garner",
year = "2010",
doi = "10.1016/j.ejps.2010.03.009",
language = "English",
volume = "40",
pages = "125--31",
journal = "Norvegica Pharmaceutica Acta",
issn = "0928-0987",
publisher = "Elsevier",
number = "2",

}

RIS

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

VL - 40

SP - 125

EP - 131

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

IS - 2

ER -

ID: 20390276