PMID: 3761165Jul 1, 1986Paper

Hepatic binding and Michaelis-Menten metabolism of drugs

Journal of Pharmaceutical Sciences
G M Rubin, T N Tozer

Abstract

Certain drugs with metabolism that obeys Michaelis-Menten kinetics are extensively bound in the liver. During the initial distribution phase after a single dose, the binding sites act as a "sink" and compete with the metabolizing enzymes for the drug. After this phase is completed, the bound sites act as a source of drug for the enzymes. Computer simulations of a perfused liver system, with well-stirred reservoir and hepatic compartments, were performed to assess whether or not such binding, as measured by the partition coefficient (Kp) between the liver and the emergent venous blood, affects the tendency to saturate metabolism. Metabolism was assumed to follow Michaelis-Menten kinetics and only unbound drug was assumed to have access to the enzymes. The value of Kp was varied to determine the effect of binding (instantaneous equilibrium) on the tendency to saturate metabolism. The effect of binding rate was also determined by adjusting the association and dissociation rate constants while maintaining a constant value of the equilibrium partition coefficient. Input into reservoir and liver were done to simulate "intravenous" and "oral" dosing, respectively. The average clearance (dose divided by the area under the reservoir con...Continue Reading

References

Dec 1, 1977·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R Stegmann, M H Bickel
Apr 1, 1973·Journal of Pharmacokinetics and Biopharmaceutics·M RowlandG G Graham
Mar 1, 1974·Chemico-biological Interactions·M H Bickel, J W Steele
Sep 1, 1984·Annals of Internal Medicine·C S Tsao
Mar 1, 1984·Journal of Pharmaceutical Sciences·P J Wedlund, G R Wilkinson
Apr 1, 1983·Journal of Pharmacokinetics and Biopharmaceutics·M S LennardH F Woods

❮ Previous
Next ❯

Citations

Jan 1, 1988·Pharmacology & Therapeutics·A MelanderA McLean
Jun 6, 2000·Advanced Drug Delivery Reviews·D D ShenK E Thummel
Mar 11, 1998·Clinical and Experimental Pharmacology & Physiology·H GhabrialD J Morgan
Aug 1, 1995·Journal of Pharmacokinetics and Biopharmaceutics·W P GengK S Pang
Feb 1, 1993·Journal of Pharmacokinetics and Biopharmaceutics·X XuK S Pang
Feb 7, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cody J PeerWilliam D Figg
Sep 27, 2012·Molecular Pharmaceutics·Helena Anna ThörnHans Lennernäs

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.