Understanding the hepatic disposition of statins to improve predictions of safety and efficacy

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2019
Thesis identifier
  • T16452
Person Identifier (Local)
  • 201574502
Qualification Level
Qualification Name
Department, School or Faculty
  • To date, little is known about the hepatic transport of statins by the multi resistance proteins MRP2, MRP3 and MRP4 or their inhibitory potential against these same carrier proteins. By inference, the potential clinical consequences of statin transport and inhibition are not fully characterised.This thesis examines seven statins, their transport properties against MRP2, MRP3 and MRP4 and their ability to act as transport inhibitors. The inside-out vesicular model was employed where only a single MRP transporter was transfected. Key findings were;Statins identified as substrates:MRP2: RosuvastatinMRP3: Pravastatin, rosuvastatinMRP4: Fluvastatin, pitavastatin, pravastatinStatins identified as inhibitors:MRP2: All statins (weak inhibitors except for lovastatin)MRP3: All statins moderate to strong inhibitors especially atorvastatinMRP4: All moderate inhibitors except pravastatin (weak)Notably, our findings imply that statins acting as perpetrators of MRP3 and MRP4 inhibition may be of more clinical relevance than their behaviour as substrates.
Advisor / supervisor
  • Taskar , Kunal
  • Gant, Helen Mary
  • MacKay, Simon
Resource Type
  • Previously held under moratorium in Chemistry Department (GSK) from 03/10/2019 to 14/12/2022