DRUG-PHYTOCHEMICAL INTERACTIONS: AN UNUSUAL IMPEDIMENT TO ACETAMINOPHEN
ABSORPTION BY PHYTOCHEMICALS OPENS UP NEW CONCERNS FOR ITS SAFETY
Abstract
Aim This study was aimed at evaluating the impact of phytochemicals of
Aframomum melegueta (Alligator pepper; AM) seeds on the bioavailability
of acetaminophen (N-acetyl-p-aminophenol; APAP) and amlodipine. Methods
The everted intestinal sac model was used to assess the transfer of
Acetaminophen and amlodipine across the GIT wall. A portion of the GIT
was excised, everted, filled with physiological solution with both ends
ligated to make a closed loop, and immersed in a beaker containing a
concentration of the test drug either alone or in the presence of AM
seed extract (AMSE). After a period of time to achieve transfer
equilibrium, the everted tissues were removed, blotted dry on an
absorbent paper and drained into a test-tube. The concentration of the
test drug was determined in these serosal fluids to assess transfer
efficiency. Results The seed extract severely inhibited the intestinal
transfer of acetaminophen by as much as 82.4% while amlodipine transfer
was enhanced up to 94.5%. Serosal concentration of acetaminophen in the
absence and presence of AMSE were 7.62 ± 0.95 µg ml-1 and 1.34 ± 0.96 µg
ml-1 (P<0.001), while that for amlodipine were 2.54 ±1.03 µg
ml-1 and 4.94 ± 0.739 µg ml-1 respectively.. Conclusion The depression
of APAP transfer was suggested to be as a result of chemical interaction
with nitric oxide produced by the interaction of the phytoestrogens in
the extract on GPCR-bound estrogen receptor. This type of interaction
may have serious health consequences.