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. Issue 5 (10th October 2021)

• Record Type: Journal Article
• Authors: Wang, Shuyao; Chen, Chun; Guan, Chi; Qiu, Liping; Zhang, Lei; Zhang, Shaofeng; Zhou, Hongyu; Du, Hongwen; Li, Chen; Wu, Yaqiong; Chang, Hang; Wang, Tao
• Is Part Of: Pharmacology research & perspectives. Volume 9:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-10
• Subjects: asymmetrically distributed -- cell metabolism -- membrane transport -- microanalysis -- unbound drug concentration; Pharmacology -- Periodicals; Drug development -- Periodicals; 615.105
• DOI: 10.1002/prp2.879
• Languages: English
• ISSNs: 2052-1707

Abstract

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 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. Abstract : Unbound concentrations of of 14 commercial drugs in rat liver, muscle, and blood