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.