TY  - JOUR
A1  - Wilson, Ian D.
A1  - Wilson, Claire E.
A1  - Scheer, Nico
A1  - Dickie, A.P.
A1  - Schreiter, K.
A1  - Wilson, E. M.
A1  - Riley, R. J.
A1  - Wehr, R.
A1  - Bial, J.
T1  - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
JF  - Biochemical pharmacology
Y1  - 2017
U6  - http://dx.doi.org/10.1016/j.bcp.2017.03.015
SN  - 1873-2968
VL  - Volume 135
SP  - 139
EP  - 150
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Wilson, C. E.
A1  - Dickie, A. P.
A1  - Schreiter, K.
A1  - Wehr, R.
A1  - Wilson, E. M.
A1  - Bial, J.
A1  - Scheer, Nico
A1  - Wilson, I. D.
A1  - Riley, R. J.
T1  - The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
JF  - Archives of Toxicology
N2  - The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
Y1  - 2018
U6  - http://dx.doi.org/10.1007/s00204-018-2212-1
SN  - 1432-0738
VL  - 92
IS  - 6
SP  - 1953
EP  - 1967
PB  - Springer
ER  - 
TY  - JOUR
A1  - Kapelyukh, Yury
A1  - Henderson, Colin James
A1  - Scheer, Nico
A1  - Rode, Anja
A1  - Wolf, Charles Roland
T1  - Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice
JF  - Drug Metabolism and Disposition
Y1  - 2019
U6  - http://dx.doi.org/10.1124/dmd.119.087718
IS  - Early view
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Henderson, Colin James
A1  - Kapelyukh, Yury
A1  - Rode, Anja
A1  - Mclaren, Aileen W.
A1  - MacLeod, Alastair Kenneth
A1  - Lin, De
A1  - Wright, Jayne
A1  - Stanley, Lesley
A1  - Wolf, C. Roland
T1  - An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials
JF  - Drug Metabolism and Disposition
Y1  - 2019
U6  - http://dx.doi.org/10.1124/dmd.119.086397
IS  - Early view
ER  -