Species | Whole Liver Intrinsic Clearance of Diclofenac Extrapolated from in Vitro Microsomal Metabolism Data | Systemic Blood Clearance of Diclofenac Extrapolated from in Vitro Microsomal Metabolism Data | In Vivo Blood Clearance of Diclofenac from Literature Data3-a | ||||||
---|---|---|---|---|---|---|---|---|---|
4′-Hydroxy Diclofenac Formation Only | AG Formation | 4′-Hydroxy Diclofenac + AG Formation | 4′-Hydroxy Diclofenac Formation Only | 4′-Hydroxy Diclofenac + AG Formation | |||||
Without Alamethicin | With Alamethicin | Without Alamethicin | With Alamethicin | Without Alamethicin | With Alamethicin | ||||
ml/min/kg | |||||||||
Rat | 180 | 77.9 | 374 | 258 | 554 | 1.6 | 2.2 | 4.6 | 183-b, 7–113-c |
Dog | 7.04 | 134 | 334 | 141 | 341 | 0.064 | 1.2 | 2.8 | 2.5–3.03-d |
Human | 252 | 173 | 748 | 425 | 999 | 2.0 | 3.2 | 6.2 | 7.63-e |
↵3-a Blood clearances were calculated from plasma clearance values reported in literature as CLblood = CLplasma/[B/P], where B/P is blood-to-plasma concentration ratio of diclofenac; a value of 0.55 was used for B/P in all species.
↵3-b Data on systemic clearance of diclofenac in vivo in rats from Peris-Ribera et al., 1991.
↵3-c Estimated hepatic blood clearance of diclofenac in isolated perfused rat liver, with physiological concentrations of protein in the perfusate (Hussein et al., 1993; Weiss et al., 2000).
↵3-d Estimated from data in Riess et al., 1978 andTsuchiya et al., 1980
↵3-e From Willis et al., 1979, 1980.