In Vitro and In Vivo Assessment of Atemoya Fruit (Annona atemoya) for Food–Drug Interactions

Background and Objectives: Atemoya (Annona atemoya) is increasingly being consumed worldwide because of its pleasant taste. However, only limited information is available concerning possible atemoya–drug interactions. In the present study, the issue of whether atemoya shows food–drug interactions with substrate drugs of the major drug-metabolizing cytochrome P450s (i.e., CYP1A2, CYP2C9, and CYP3A) is addressed. Methods: The ability of atemoya juice to inhibit the activities of phenacetin O-deethylase (CYP1A2), diclofenac 4′-hydroxylase (CYP2C9), and midazolam 1′-hydroxylase (CYP3A) was examined in vitro using human and rat liver microsomes. The in vivo pharmacokinetics of phenacetin and metabolites derived from it in rats when atemoya juice or fluvoxamine (a CYP1A2 inhibitor) was preadministered were also investigated. Results: Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A. In spite of this inhibition, preadministration of atemoya had no effect on the pharmacokinetics of phenacetin, a CYP1A2 substrate, in rats. Meanwhile, preadministration of fluvoxamine significantly extended the time needed for the elimination of phenacetin, possibly due to the inhibition of CYP1A2. This suggests that the intake of an excess amount of atemoya juice is necessary to cause a change in the pharmacokinetics of phenacetin when the IC₅₀ values for CYP1A2 inhibition by atemoya and fluvoxamine are taken into account. Conclusion: The results indicate that a daily intake of atemoya would not change the pharmacokinetics of CYP1A2 substrates such as phenacetin as well as CYP2C9- and CYP3A-substrate drugs.