Estimation of CLint,in vivo from in vivo pharmacokinetic data for model compounds in rats and humans
Compounds | Species | CLoral or CLtot | Fa | fp | RB | CLint,in vivo | EH | Metabolic Pathway | Reference | |
---|---|---|---|---|---|---|---|---|---|---|
Well stirred | Dispersion | |||||||||
ml/min/kg body weight | ml/min/kg body weight | |||||||||
FK1052 | Rat | 8752-a | 0.95 | 0.03 | 1.21 | 27,700 | 7,950 | 0.93 | Oxidation | In house data |
Human | 26.42-a | 0.016 | 0.78 | 1,570 | 1,070 | 0.61 | ||||
FK480 | Rat | 81.12-a | 0.70 | 0.01 | 0.626 | 5,680 | 3,820 | 0.62 | Oxidation | In house data |
Human | 2.42-a | 0.005 | 0.6 | 336 | 321 | 0.12 | ||||
Diazepam | Rat | 103.82-a | 1.00 | 0.137 | 1.04 | 758 | 496 | 0.64 | Oxidation | Diaz-Garcia et al. (1992), Luurila et al. (1996), |
Human | 0.72-a | 0.032 | 1.04 | 21.9 | 21.5 | 0.03 | Navia and Chaturvedi (1996), Sawada et al. (1985), Klotz et al. (1976) | |||
Diltiazem | Rat | 300.22-a | 1.00 | 0.184 | 0.93 | 1,630 | 685 | 0.85 | Oxidation | Tsui et al. (1994), Kölle et al. (1983) |
Human | 64.22-a | 0.22 | 1.0 | 292 | 160 | 0.76 | Levet-Trafit et al. (1996), Lee et al. (1992), Piepho et al. (1982) | |||
Quinotolast | Rat | 27.92-b | 1.00 | 0.033 | 0.65 | 574 | 489 | 0.35 | Oxidation, glucuronidation | Katashima et al. (1993a,b) |
Human | 1.232-a | 0.0191 | 0.59 | 64.4 | 62.2 | 0.09 | Nakashima et al. (1993), in house data | |||
Troglitazone | Rat | 21.52-b | 0.718 | 0.000921 | 0.594 | 67,800 | 43,700 | 0.66 | Glucuronidation, sulfation | Izumi et al. (1996) |
Human | 13.12-a | 0.000941 | 0.548 | 10,000 | 7,910 | 0.45 | ||||
FK079 | Rat | 1.642-b | 1.00 | 0.060 | 0.63 | 28.8 | 28.3 | 0.05 | Oxidation, hydrolysis | Tokuda et al. (1997) |
Human | 10.822-a | 0.017 | 0.59 | 636 | 497 | 0.22 | ||||
Zidovudine | Rat | 40.672-b | 1.00 | 0.786 | 1.0 | 20.2 | 18.4 | 0.22 | Glucuronidation, oxidation | Mays et al., (1991), de Miranda et al., (1990) |
Human | 39.122-a | 0.8 | 0.98 | 42.1 | 28.4 | 0.62 | Yazdanian et al. (1998), Blum et al., (1988), Collins and Unadkat, (1989), Hedaya et al., (1990) | |||
Acetaminophen | Rat | 23.82-b | 1.00 | 0.82 | 1.0 | 51.0 | 41.0 | 0.43 | Glucuronidation, sulfation | Hjelle and Klaassen, (1984), Koss et al., (1970) |
Human | 4.652-b | 0.79 | 1.0 | 6.71 | 6.17 | 0.20 | Gazzard et al. (1973), Chiou and Barve (1998), Sonne et al. (1988), Lin and Levy (1986) |