Disposition of prednisone and prednisolone in the perfused rabbit liver: Modeling hepatic metabolic processes

@article{Hale2005DispositionOP,
  title={Disposition of prednisone and prednisolone in the perfused rabbit liver: Modeling hepatic metabolic processes},
  author={V. G. Hale and Kazumasa Aizawa and Lewis B. Sheiner and Leslie Z. Benet},
  journal={Journal of Pharmacokinetics and Biopharmaceutics},
  year={2005},
  volume={19},
  pages={597-614}
}
  • V. Hale, K. Aizawa, L. Benet
  • Published 1 October 1991
  • Biology, Medicine
  • Journal of Pharmacokinetics and Biopharmaceutics
The livers of 15 rabbits were perfused in situwith prednisone (PO) or prednisolone (POH) over a wide range of steady state concentrations, resulting in multiple experimental measurements per organ. Linearity of extraction, an apparent lack of oxidative conversion, and marked preference for the reduction of PO to POH was observed. Predictions of hepatic tissue concentrations were made using both the well-stirred and parallel-tube model approximations. Giucocorticoid disposition across the liver… 
1 Citations

References

SHOWING 1-10 OF 39 REFERENCES
Prednisone and prednisolone interconversion in the rabbit utilizing unbound concentrations
TLDR
Although saturability in the formation of PO from POH was noted, this nonlinear step is apparently not large enough to induce observable changes from linearity in the overall disposition of unbound POH.
Prednisolone clearance at steady state in dogs.
TLDR
To determine in dogs under steady-state conditions whether prednisolone clearance increases with increasing dose as has been suggested from results obtained under nonsteady- state conditions in man, and whether the predisonsolone to prednisone conversion, apparently resulting from 11 beta-hydroxydehydrogenase, is saturable.
Flow dependence of propranolol elimination in perfused rat liver.
TLDR
In 13 of 14 experiments, increasing the flow rate resulted in a decrease of the inlet concentration and elevation of the outlet concentration, which reject the venous equilibration model but are consistent with the sinusoidal perfusion model under the experimental conditions investigated.
Dose‐dependent pharmacokinetics of prednisone and prednisolone in man
TLDR
The apparent clearance values indicate that the dose-dependent effect occurs following oral administration of prednisone, and are in good agreement with those reported by Pickup & others (1977).
Hepatic transport kinetics and plasma disappearance curves: distributed modeling versus conventional approach.
TLDR
A distributed model that takes account of intrahepatic concentration profiles, nonuniform blood-flow distribution in the sinusoids, and delayed mixing in the peripheral circulation is constructed, indicating that conventional estimates of the rate constants for hepatic uptake and cell-to-plasma efflux are subject to a systematic underestimate.
A dispersion model of hepatic elimination: 1. Formulation of the model and bolus considerations
TLDR
A dispersion model of hepatic elimination, based on the residence time distribution of blood elements within the liver, is presented and is shown to be compatible with the known hepatic architecture and hepatic physiology.
Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance
  • K. PangM. Rowland
  • Biology, Medicine
    Journal of Pharmacokinetics and Biopharmaceutics
  • 2005
TLDR
Although both models predict similar hepatic drug clearances under a variety of conditions, marked differences between them become apparent in their predictions of the influence of changes in the determinants of drug clearance on various pharmacokinetic parameters.
Dose dependent pharmacokinetics of prednisone and prednisolone in man
TLDR
It is indicated that the pharmacokinetic parameters of protein-free and transcortin-free prednisolone were relatively constant with dose and that protein binding does not fully explain their apparent nonlinear distribution and disposition.
...
...