Open AccessEffects 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
Author(s) -
Wang Shuyao,
Chen Chun,
Guan Chi,
Qiu Liping,
Zhang Lei,
Zhang Shaofeng,
Zhou Hongyu,
Du Hongwen,
Li Chen,
Wu Yaqiong,
Chang Hang,
Wang Tao
Publication year - 2021
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.879
Subject(s) - efflux , microdialysis , transporter , metabolism , skeletal muscle , chemistry , drug metabolism , pharmacology , membrane transport , biochemistry , extracellular , endocrinology , biology , membrane , gene
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 puu,liver and K puu,muscle 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.