Metabolite pharmacokinetics: The area under the curve of metabolite and the fractional rate of metabolism of a drug after different routes of administration for renally and hepatically cleared drugs and metabolites
- 1 August 1981
- journal article
- research article
- Published by Springer Nature in Journal of Pharmacokinetics and Biopharmaceutics
- Vol. 9 (4), 477-487
- https://doi.org/10.1007/bf01060890
Abstract
A model comprised of four compartments, a central and liver compartment for a drug, and a central and liver compartment for a metabolite, is presented to describe the interrelationships between the area under the curve of the metabolite and physiological parameters after intravenous and intraportal administration of the drug. The model includes renal and hepatic eliminatory mechanisms for both drug and metabolite as long as the metabolite is formed only by the liver. It is found that when competing renal eliminatory pathways exist for a drug, the area under the curve for the metabolite will change according to the route of drug administration. Also, the fractional rate of metabolism of a drug to form the metabolite will be underestimated by the normal use of the ratio areas under the curve of the metabolite. Other properties of the model are also discussed.This publication has 14 references indexed in Scilit:
- Prediction of steady-state behavior of metabolite from dosing of parent drugJournal of Pharmaceutical Sciences, 1980
- Sequential first-pass elimination of a metabolite derived from a precursorJournal of Pharmacokinetics and Biopharmaceutics, 1979
- Disposition kinetics in dogs of diethyldithiocarbamate, a metabolite of disulfiramJournal of Pharmacokinetics and Biopharmaceutics, 1978
- A theoretical examination of the effects of gut wall metabolism, hepatic elimination, and enterohepatic recycling on estimates of bioavailability and of hepatic blood flowJournal of Pharmacokinetics and Biopharmaceutics, 1978
- Hepatic clearance of drugs. III. Additional experimental evidence supporting the “wellstirred” model, using metabolite (MEGX) generated from lidocaine under varying hepatic blood flow rates and linear conditions in the perfused rat liverin situ preparationJournal of Pharmacokinetics and Biopharmaceutics, 1977
- Pharmacokinetics of isoniazid and some metabolites in manJournal of Pharmacokinetics and Biopharmaceutics, 1976
- Utilization of area under the curve to elucidate the disposition of an extensively biotransformed drugJournal of Pharmacokinetics and Biopharmaceutics, 1973
- Pharmacokinetic Model for Chlordiazepoxide·HCl in the DogJournal of Pharmaceutical Sciences, 1970
- Two-Compartment Model for a Drug and Its Metabolite: Application to Acetylsalicylic Acid PharmacokineticsJournal of Pharmaceutical Sciences, 1970
- Pharmacokinetics of Acetylsalicylic Acid and Salicylic Acid After Intravenous Administration in ManJournal of Pharmaceutical Sciences, 1968