Estimation of CLint, in vivo from in vivo pharmacokinetic data for the model compounds in rats, dogs, and humans
Compounds | Species | CLoral or CLtot | Fa | fp | RB | CLint, in vivo | EH | Reference | ||
---|---|---|---|---|---|---|---|---|---|---|
Well Stirred | Parallel-Tube | Dispersion | ||||||||
ml/min/kg body weight | ml/min/kg body weight | |||||||||
FK1052 | Rat | 875 | 0.95 | 0.03 | 1.21 | 27708.33 | 5785.60 | 7952.74 | 0.93 | In house data |
Dog | 62.7 | 0.017 | 0.82 | 3503.82 | 1802.28 | 2114.04 | 0.70 | |||
Human | 26.4 | 0.016 | 0.78 | 1567.50 | 945.95 | 1071.18 | 0.61 | |||
FK480 | Rat | 81.1 | 0.70 | 0.01 | 0.626 | 5677.00 | 3358.32 | 3824.30 | 0.62 | In house data |
Dog | 6.6 | 0.006 | 0.6 | 770.00 | 687.51 | 709.16 | 0.20 | |||
Human | 2.4 | 0.005 | 0.6 | 336.00 | 315.14 | 320.79 | 0.12 | |||
Zolpidem | Rat | 106 | 0.89 | 0.13 | 0.89 | 725.69 | 405.00 | 466.88 | 0.66 | Ishibashi et al. (1993a,b) |
Human | 7.1 | 0.04 | 0.66 | 157.98 | 129.84 | 137.31 | 0.32 | Kudo et al. (1990) | ||
Omeprazole | Rat | 710 | 1.00 | 0.125 | 0.78 | 5680.00 | 985.69 | 1393.01 | 0.94 | Watanabe et al. (1994) |
Dog | 6.32-a | 0.097 | 0.60 | 98.38 | 79.36 | 84.03 | 0.34 | Regårdh et al. (1985) | ||
Human | 22.2 | 0.042 | 0.62 | 528.57 | 306.86 | 350.73 | 0.63 | Andersson et al. (1990) | ||
Nicardipine | Rat | 1212 | 1.00 | 0.084 | 1.02-b | 14428.57 | 2059.22 | 2992.55 | 0.96 | Higuchi and Shiobara (1980a,b) |
Dog | 597 | 0.062 | 1.02-b | 9629.03 | 1500.95 | 2154.28 | 0.95 | |||
Human | 131 | 0.068 | 1.02-b | 1926.47 | 606.32 | 779.70 | 0.86 | |||
Nilvadipine | Rat | 2852 | 1.00 | 0.0117 | 0.922 | 243760.68 | 17589.94 | 27932.16 | 0.98 | Tokuma et al. (1987, 1988) |
Dog | 36 | 0.008 | 0.836 | 4500.00 | 2818.31 | 3170.52 | 0.58 | Terakawa et al. (1988) | ||
Human | 107 | 0.013 | 0.789 | 8230.77 | 2539.97 | 3277.20 | 0.87 | Niwa et al. (1987); in house data | ||
Diazepam | Rat | 103.8 | 1.00 | 0.137 | 1.04 | 757.66 | 432.66 | 496.31 | 0.64 | Diaz-Garcia et al. (1992); Luurila et al. (1996) |
Human | 0.7 | 0.032 | 1.04 | 21.88 | 21.53 | 21.53 | 0.03 | Navia and Chaturvedi (1996); Sawada et al. (1985);Klotz et al. (1976) | ||
Diltiazem | Rat | 300.2 | 1.00 | 0.184 | 0.93 | 1631.52 | 536.77 | 684.98 | 0.85 | Tsui et al. (1994); Etoh et al. (1983) |
Dog | 201.6 | 0.298 | 1.02-b | 676.54 | 209.27 | 269.91 | 0.87 | Kölle et al. (1983); Levet-Trafit et al. (1996) | ||
Human | 64.2 | 0.22 | 1.0 | 291.82 | 132.79 | 159.59 | 0.76 | Lee et al. (1992); Piepho et al. (1982) |