Table 1

Pharmacokinetic parameters for DEB and 4-OH-DEB after a single oral administration of DEB (2.5 mg/kg) in wild-type, CYP2D6humanized heterozygous, and CYP2D6 humanized homozygous mice

ParameterWild TypeHeterozygousHomozygous
DEB
T max(h)2.5  ± 1.86.7  ± 0.74.6  ± 1.8
C max (nM)2,937  ± 795879  ± 1281-150 467  ± 611-150 1-159
 AUC0–24 hrs (nM · )28,393  ± 18408,757  ± 12151-150 4,634  ± 13481-150 1-159
 CL (l/h/kg)15.2  ± 0.948.9  ± 6.41-150 94.1  ± 22.31-150 1-159
 T1/2(h)16.5  ± 4.58.9  ± 2.11-150 6.9  ± 1.61-150
4-OH-DEB
T max(h)1.7  ± 0.33.3  ± 2.30.8  ± 1.2
C max (nM)110  ± 12535  ± 791-150 1075  ± 971-150 1-159
 AUC0–24 hrs (nM · )1,086  ± 284,627  ± 3771-150 9,289  ± 9311-150 1-159

Values represent the mean and the S.E.M. from three to four mice.

    • 1-150 , values from CYP2D6 humanized mice that are significantly different (p < 0.05) from wild-type mice.

    • 1-159 , values from CYP2D6 humanized homozygous mice that are significantly different (p < 0.05) fromCYP2D6 humanized heterozygous mice (p < 0.05).