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Effects of membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver of drugs: A microdialysis study in rats.
- Source :
-
Pharmacology research & perspectives [Pharmacol Res Perspect] 2021 Oct; Vol. 9 (5), pp. e00879. - Publication Year :
- 2021
-
Abstract
- The unbound concentrations of 14 commercial drugs, including five non-efflux/uptake transporter substrates-Class I, five efflux transporter substrates-class II and four influx transporter substrates-Class III, were simultaneously measured in rat liver, muscle, and blood via microanalysis. K <subscript>puu,liver</subscript> and K <subscript>puu,muscle</subscript> were calculated to evaluate the membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver. For Class I compounds, represented by antipyrine, unbound concentrations among liver, muscle and blood are symmetrically distributed when compound hepatic clearance is low. And when compound hepatic clearance is high, unbound concentrations among liver, muscle and blood are asymmetrically distributed, such as Propranolol. For Class II and III compounds, overall, the unbound concentrations among liver, muscle, and blood are asymmetrically distributed due to a combination of hepatic metabolism and efflux and/or influx transporter activity.<br /> (© 2021 Pharmaron Beijing Co Ltd. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Antipyrine blood
Antipyrine metabolism
Atenolol blood
Atenolol metabolism
Carbamazepine blood
Carbamazepine metabolism
Digoxin blood
Digoxin metabolism
Diltiazem blood
Diltiazem metabolism
Diphenhydramine blood
Diphenhydramine metabolism
Drug Elimination Routes
Gabapentin blood
Gabapentin metabolism
Lamotrigine blood
Lamotrigine metabolism
Memantine blood
Memantine metabolism
Microdialysis
Ofloxacin blood
Ofloxacin metabolism
Pharmaceutical Preparations blood
Propranolol blood
Propranolol metabolism
Pyrilamine blood
Pyrilamine metabolism
Quinidine blood
Quinidine metabolism
Rats
Terfenadine analogs & derivatives
Terfenadine blood
Terfenadine metabolism
Cell Membrane metabolism
Liver metabolism
Membrane Transport Proteins metabolism
Muscle, Skeletal metabolism
Pharmaceutical Preparations metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2052-1707
- Volume :
- 9
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Pharmacology research & perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 34628723
- Full Text :
- https://doi.org/10.1002/prp2.879