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Grapefruit juice inhibit esterase enzyme. A possible interaction with ester prodrugs should be taken into consideration. In this study, influence of grapefruit juice on sacubitril (SAC) rat liver S9 activation by esterase enzyme was evaluated. A RP-HPLC method was developed and validated for estimation of SAC in rat liver S9 fraction using C Cyano column as stationary, acetonitrile: sodium di-hydrogen phosphate buffer (0.02 M, pH 4 adjusted by o-phosphoric acid) (40: 60, v/v), as mobile phase at flow rate 1 ml/min and UV detection at 254 nm. The method was successfully applied to in vitro study in which SAC was incubated with rat liver S9 fraction prepared from rats that previously ingested grape fruit juice for a week. The calculated SAC concentration after incubation was compared with that of SAC incubated with rat liver S9 fraction of rat control group. The statistical significance between results of test and control incubation sets was assessed. In conclusion, the current study demonstrated that grapefruit juice decreased SAC hydrolysis, hence delayed 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 cautiously in patients receiving SAC.
This article was published in the following journal.
Name: Biomedical chromatography : BMC
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A self-evaluation of health status.
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