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

  • Teresa Heslop

Student thesis: Master's Thesis


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.
Date of Award3 Oct 2019
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorMary Grant (Supervisor) & Simon MacKay (Supervisor)

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