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Grapefruit juice inhibits esterase enzyme. Therefore, a possible interaction with ester prodrugs should be taken into consideration. In this study, the influence of grapefruit juice on sacubitril (SAC) rat liver S9 activation by esterase enzyme was evaluated. An RP‐HPLC method was developed and validated for estimation of SAC in rat liver S9 fraction using a C18 Cyano column as stationary phase and acetonitrile–sodium di‐hydrogen phosphate buffer (0.02 m, pH 4 adjusted by o‐phosphoric acid, 40:60, v/v), as mobile phase at a flow rate of 1 mL/min and UV detection at 254 nm. The method was successfully applied to an in vitro study in which SAC was incubated with rat liver S9 fraction prepared from rats that had previously ingested grapefruit juice for a week. The calculated SAC concentration after incubation was compared with that of SAC incubated with rat liver S9 fraction from the rat control group. The statistical significance between the results of test and control incubation sets was assessed. In conclusion, the current study demonstrated that grapefruit juice decreased SAC hydrolysis, hence delaying its activation to sacubitrilat (active form) in gut lumen. Based on this food–drug interaction, it may be required that grapefruit juice should be consumed with caution in patients receiving SAC.
Biomedical Chromatography – Wiley
Published: Aug 1, 2019
Keywords: ; ; ; ;
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