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
Parameter | Wild Type | Heterozygous | Homozygous |
---|---|---|---|
DEB | |||
T max(h) | 2.5 ± 1.8 | 6.7 ± 0.7 | 4.6 ± 1.8 |
C max (nM) | 2,937 ± 795 | 879 ± 1281-150 | 467 ± 611-150 1-159 |
AUC0–24 hrs (nM · ) | 28,393 ± 1840 | 8,757 ± 12151-150 | 4,634 ± 13481-150 1-159 |
CL (l/h/kg) | 15.2 ± 0.9 | 48.9 ± 6.41-150 | 94.1 ± 22.31-150 1-159 |
T1/2(h) | 16.5 ± 4.5 | 8.9 ± 2.11-150 | 6.9 ± 1.61-150 |
4-OH-DEB | |||
T max(h) | 1.7 ± 0.3 | 3.3 ± 2.3 | 0.8 ± 1.2 |
C max (nM) | 110 ± 12 | 535 ± 791-150 | 1075 ± 971-150 1-159 |
AUC0–24 hrs (nM · ) | 1,086 ± 28 | 4,627 ± 3771-150 | 9,289 ± 9311-150 1-159 |
Values represent the mean and the S.E.M. from three to four mice.