Drug Metabolizing Enzyme CYP1A2 Status in Pediatric Patients with Hemoglobin E-βββββ Thalassemia
Laddawan Senggunprai MSc*, Upa Kukongviriyapan PhD**, Arunee Jetsrisuparb MD***, Veerapol Kukongviriyapan PhD*
Affiliation : * Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand ** Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand *** Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Objective : To evaluate the drug metabolizing enzyme CYP1A2 activity in pediatric hemoglobin E-beta-
thalassemia patients, since CYP1A2 is responsible for the metabolism of a number of drugs. Alteration of its
activity may have clinical consequences.
Material and Method: Twenty-three hemoglobin E-beta thalassemia pediatric patients and 24 age-matched
controls were recruited in the present study. Caffeine in the form of a soft drink was orally administered as a
test probe for CYP1A2 activity. Plasma collected at pre-dose and 6 hr after intake was analyzed for the levels
of caffeine and paraxanthine, its major metabolite to represent the activity of CYP1A2.
Results : Biochemical markers, including blood glutathione and urinary lipid hydroperoxides indicated that
patients were in an oxidant stress state. The plasma ratio of paraxanthine to caffeine was unchanged between
patients and controls. Multiple regression analysis revealed that gender and the liver enzyme were the
significant determinants of CYP1A2 activity (adjusted r2 = 0.48, p < 0.001). Male gender was associated with
higher activity of CYP1A2 activity.
Conclusion : The CYP1A2 activity is not apparently changed in thalassemia patients despite the presence of
an oxidative stress state.
Keywords : Thalassemia, Oxidative stress, CYP1A2, Cytochrome p450
