Table 3

Extrapolation of 4′-hydroxy diclofenac and acyl glucuronide formation kinetic data in rat, dog, and human liver microsomes to whole liver (CLEmbedded Image ) and systemic blood clearance of diclofenac in these species

SpeciesWhole Liver Intrinsic Clearance of Diclofenac Extrapolated from in Vitro Microsomal Metabolism DataSystemic Blood Clearance of Diclofenac Extrapolated from in Vitro Microsomal Metabolism DataIn Vivo Blood Clearance of Diclofenac from Literature Data3-a
4′-Hydroxy Diclofenac Formation OnlyAG Formation4′-Hydroxy Diclofenac + AG Formation4′-Hydroxy Diclofenac Formation Only4′-Hydroxy Diclofenac + AG Formation
Without AlamethicinWith AlamethicinWithout AlamethicinWith AlamethicinWithout AlamethicinWith Alamethicin
ml/min/kg
Rat18077.93742585541.62.24.6183-b, 7–113-c
Dog7.041343341413410.0641.22.82.5–3.03-d
Human2521737484259992.03.26.27.63-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.