Drug metabolizing enzyme CYP1A2 status in pediatric patients with hemoglobin E-beta thalassemia.
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.


METHODS
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 CYPIA2.


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.


CONCLUSIONS
The CYP1A2 activity is not apparently changed in thalassemia patients despite the presence of an oxidative stress state.
Senggunprai
Laddawan
L
Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Kukongviriyapan
Upa
U
Jetsrisuparb
Arunee
A
Kukongviriyapan
Veerapol
V
D002110:Caffeine / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D016001:Confidence Intervals; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000097:blood; D005978:Glutathione / Q000097:blood; D006446:Hemoglobin E / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000652:urine; D008099:Liver / Q000201:enzymology*; D008297:Male; D015999:Multivariate Analysis; D018384:Oxidative Stress; D012737:Sex Factors; D013785:Thailand / Q000453:epidemiology; D013806:Theophylline / Q000097:blood; D000637:Transaminases / Q000097:blood; D017086:beta-Thalassemia / Q000201:enzymology* / Q000453:epidemiology
D008054:Lipid Peroxides; D002110:Caffeine; D005293:Ferritins; D006446:Hemoglobin E; D013806:Theophylline; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D000637:Transaminases; D005978:Glutathione; C021183:1,7-dimethylxanthine