biostudies-literatureZhu HJAmerican Association of Colleges of PharmacyNCATS NIH HHSNIA NIH HHSNational Center for Advancing Translational Sciences of the National Institutes of HealthNational Institute on AgingNIGMS NIH HHS681-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC4865408biostudies-literatureUnknown72(6)<h4>Purpose</h4>The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant -816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant -816A>C on the activation of the ACEI prodrug trandolapril in human livers and the blood pressure (BP)-lowering effect of trandolapril in hypertensive patEuropean journal of clinical pharmacologyCES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril.PMC4865408R21AG048500R21 AG048500UL1 TR002240U01 GM0744922015 New Investigator Award2UL1TR000433UL1 TR000433Langaee TYZhu HJJohnson JAWang XMarkowitz JSGong YPepine CJCooper-DeHoff RMfalseCES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril.<h4>Purpose</h4>The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant -816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant -816A>C on the activation of the ACEI prodrug trandolapril in human livers and the blood pressure (BP)-lowering effect of trandolapril in hypertensive pat2016-01-01T00:00:00Z2016 Jun2026-05-30T02:29:29.375Z2019-03-27T02:13:33ZS-EPMC48654082691581310.1007/s00228-016-2029-x