TABLE 4

Kp,brain values in mdr 1a(-/-) and mdr 1a(+/+) mice after intravenous injection of various drugs

Time after administration mdr1a(+/+) mdrla(-/-) Ratio (Kp,brain,ko/Kp,brain,wt) Reference
Plasma Conc. (ng/ml) Brain Conc. (ng/ml) Kp,brain Plasma Conc. (ng/ml) Brain Conc. (ng/ml) Kp,brain
Asimadolinea 1 h 211 65 0.31 199 586 2.94 9.56 Jonker et al., 1999
Azasetron 0.119 0.833 7.0 Tamai and Tsuji, 2000
Carebastin 0.0403 0.319 7.9 Tamai and Tsuji, 2000
Cyclosporine 4 h 38 10.5 0.28 54 178 3.3 12 Schinkel et al., 1995b
Daunomycin 30 min 0.91 1.63 1.8 Adachi et al., 2001
Dexamethasone 4 h 17.2 4.9 0.28 17.2 12.1 0.7 2.5 Schinkel et al., 1995b
Diazepam 30 min 3.35 3.24 0.9 Adachi et al., 2001
Digoxin 4 h 669 55.5 0.08 1259 1939 1.5 19 Schinkel et al., 1995b
Digoxin 90 min 21.2 1.1 0.05 39.6 21.1 0.53 10.3 Mayer et al., 1997
Digoxin a 4 h 622 37.1 0.06 1775 1011 0.57 9.5 Schinkel et al., 1997
Doxorubicin 1 h 0.00077 0.0025 3.2 Kusuhara and Sugiyama, 2001a
Ebastine 0.114 0.846 7.4 Tamai and Tsuji, 2000
Grepafloxacina, b 2 h 0.34 1 2.9 Tamai et al., 2000b
HSR903 2 h 0.38 2.85 7.5 Murata et al., 1999
Indinavir 4 h 19 1.6 0.08 21 17 0.81 10 Kim et al., 1998
Ivermectinc 4 h 22 0.9 0.041 70 41 0.586 14.3 Schinkel et al., 1995a
Ivermectinc 24 h 16 1.5 0.094 52 131 2.519 26.9 Schinkel et al., 1994
Loperamidec 4 h 13.3 4.1 0.31 26.7 55.3 2.1 6.7 Schinkel et al., 1996
Morphine 4 h 10.9 5.3 0.49 12.4 8.9 0.72 1.48 Schinkel et al., 1995b
Nelfinavir 4 h 14 1.2 0.09 17 45 2.65 31 Kim et al., 1998
Ondansetron 30 min 40.5 18.7 0.46 39.4 75.6 1.92 4.2 Schinkel et al., 1996
Progesterone 30 min 1.45 1.34 0.9 Adachi et al., 2001
Quinidine 10 min 0.17 4.64 28 Kusuhara et al., 1997
Rhodamine-123 4 h 2.55 0.54 0.21 2.84 2.81 0.99 4.66 de Lange et al., 1998
Saquinavir 4 h 31 4.1 0.13 34 30 0.88 6.67 Kim et al., 1998
Sparfloxacina, b 2 h 0.14 0.54 3.9 Tamai et al., 2000b
Tacrolimus 5 h 2.73 16.4 6.1 Yokogawa et al., 1999
Valspodar 4 h 0.6 1.2 2 Desrayaud et al., 1998
Verapamil 1 h 35 15 0.42 43 142 3.3 7.9 Hendrikse et al., 1998
Vinblastine 4 h 3 5 1.7 6 112 18.7 11 Schinkel et al., 1994
Vincristine 0.027 0.066 2.4 Tamai and Tsuji, 2000

  • Drugs were administered intravenously to both wild-type and mdr 1a or mdr 1a/1b double knockout mice. Plasma and brain concentrations were determined at the time of death. Kp,brain was obtained by dividing the brain concentration by the plasma concentration.

  • ↵ a Mdr 1a/mdr 1b double knockout mice were used for this experiment.

  • ↵ b Kp,brain values of grepafloxacin and sparfloxacin were evaluated using plasma unbound concentration.

  • ↵ c Oral administration.