Evaluation of hepatic function using the pharmacokinetics of a therapeutically administered drug. Application to the immunosuppressant cyclosporin.
A method is presented for the simultaneous estimation of functional hepatic blood flow and intrinsic clearance. The method uses pharmacokinetic data of a therapeutically employed drug and one of its primary metabolites following intravenous and oral administration of the parent compound. When the disposition of the drug is linear, this method can cope with complicated dosage regimens commonly confronted in clinical data. The feasibility of the method was demonstrated in 10 patients who had undergone liver transplantation and were receiving cyclosporin in the immediate postoperative period. Mean hepatic blood flow was estimated to be 0.89 (95% CI: 0.62 to 1.23) L/h/kg and intrinsic cyclosporin clearance as 0.60 (95% CI: 0.49 to 0.72) L/h/kg. Apart from the hepatic parameters, bioavailability and the fraction of the dose absorbed, a detailed pharmacokinetic description of the parent drug and the elimination pharmacokinetics of a primary metabolite are provided. This information not only allows optimisation of individual therapy, but also may be used to compare absorption properties of different pharmaceutical formulations.
Weber
W
W
Institute of Clinical Pharmacology, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany.
Looby
M
M
Brockmöller
J
J
D000284:Administration, Oral; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007165:Immunosuppression Therapy; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D016031:Liver Transplantation; D008657:Metabolic Clearance Rate
D016572:Cyclosporine