Models of hepatic drug clearance: discrimination between the 'well stirred' and 'parallel-tube' models.
The predictive ability of two models of hepatic drug clearance are compared. The 'parallel-tube' model predicts that the steady-state drug concentration following constant rate oral administration increases with increase in hepatic blood flow. The 'well-stirred' model predicts that this parameter is not sensitive to changes in hepatic blood flow. Using the steady-state reservoir drug concentration as the discriminatory index, the predictions of the models were tested in a recirculating isolated perfused rat liver system with lignocaine and pethidine, both of which are highly extracted, as test drugs. The steady-state reservoir concentration of both drugs was found to be constant when flow through the liver was increased from 10 ml min-1 to 15 ml min-1. The experimental findings indicate that the 'well-stirred' model more accurately describes the elimination of highly cleared drugs with perturbations of flow than does the 'parallel-tube' model.
D000818:Animals; D066298:In Vitro Techniques; D008012:Lidocaine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D008614:Meperidine / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004364:Pharmaceutical Preparations; D008012:Lidocaine; D008614:Meperidine