Monitoring in situ liver metabolism in rats using microdialysis. Comparison of microdialysis mass-transport model predictions to experimental metabolite generation data

Journal of Pharmaceutical Sciences
J A StenkenM Z Southard

Abstract

The generation of metabolites from two model compounds, phenacetin and acetaminophen, included in the perfusion fluid of a microdialysis probe implanted into rat liver was studied. When 60 microM phenacetin was included in the perfusion fluid using a flow rate of 1.0 microL/min, acetaminophen and acetaminophen sulfate were recovered at concentrations that ranged between 0.4 and 1.6 microM. Acetaminophen sulfate ([AS]gain) diffused back into the microdialysis probe on a micromolar percentage basis of 8.9+/-2.4% (n = 3) when acetaminophen was passed through the probe at a concentration between 11 and 12 microM. When 220-240 microM acetaminophen was passed through the probe, the percentage of acetaminophen sulfate recovered was 4.8+/-1.4% (n = 3) (P < 0.1 compared to the 11 microM group). No acetaminophen glucuronide was detected in the dialysate samples. A mathematical model that describes mass transport in microdialysis sampling was used to predict the concentration of metabolite that could be recovered into the dialysate after the loss of a substrate compound that undergoes metabolism. The model predicts a metabolite recovery of 23.6% using estimates for phenacetin metabolism and 21.5% using estimates for acetaminophen metaboli...Continue Reading

References

Nov 15, 1979·Biochemical Pharmacology·D J Miner, P T Kissinger
Jul 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C A GoreskyG G Bach
Jan 1, 1991·Trends in Neurosciences·J Olesen, L Edvinsson
Oct 1, 1991·Journal of Internal Medicine·U Ungerstedt
Apr 15, 1988·Biochemical Pharmacology·L Bass, S Keiding
May 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G J GoresN F LaRusso
Jul 15, 1981·Biochemical Pharmacology·K S Pang, J A Terrell
Aug 1, 1995·Journal of Applied Physiology·R C HicknerJ Henriksson
Nov 1, 1994·Pharmaceutical Research·J M AultC E Lunte
Jan 1, 1993·European Journal of Drug Metabolism and Pharmacokinetics·L Ståhle
Mar 1, 1996·Analytical Chemistry·P M Sam, J B Justice
Apr 1, 1958·The Anatomical Record·A M RAPPAPORT

❮ Previous
Next ❯

Citations

Jul 29, 1999·Biomedical Chromatography : BMC·C S Chaurasia
Mar 10, 2001·Analytical Biochemistry·J A StenkenL Sun
Jun 8, 2001·Journal of Pharmacological and Toxicological Methods·L SasongkoA J McLachlan
Jul 6, 2007·Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)·Hong ZhengJin-Hong Hu
May 16, 2015·The Analyst·David W Paul, Julie A Stenken

❮ 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.