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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&gt;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&gt;C on the activation of the ACEI prodrug trandolapril in human livers and the blood pressure (BP)-lowering effect of trandolapril in hypertensive patients.

CES1P1 variant −816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril