Activities of cytochrome P450 1A2, N-acetyltransferase 2, xanthine oxidase, and cytochrome P450 2D6 are unaltered in children with cystic fibrosis.
The activities of hepatic cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT-2), xanthine oxidase (XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis (CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Subjects were given 4 oz of Coca-Cola (approximately 35 mg caffeine) (The Coca-Cola Company, Atlanta, Ga) and a single 0.5-mg/kg dose of dextromethorphan. Urine was collected for 8 hours after biomarker administration, and enzyme activity was assessed by use of previously validated caffeine and dextromethorphan molar ratios. CYP2D6 genotyping was also performed in 10 of 12 subjects with CF and 11 of 12 control subjects. There were no significant differences in the urinary molar ratios for any of the enzyme systems evaluated. These data suggest that CF does not alter the activities of CYP1A2, NAT-2, XO, and CYP2D6. Altered biotransformation of drugs in this patient population is likely enzyme- and isoform-specific and thus is apparent for only selected compounds that are substrates for enzymes other than CYP1A2, NAT-2, XO, and CYP2D6.
Division of Pediatric Clinical Pharmacology and Medical Toxicology, The Children's Mercy Hospitals and Clinics, Kansas City, MO, USA. mjkenn07@louisville.edu
Mary Jayne
MJ
Kennedy
Charity D
CD
Scripture
Angela D M
AD
Kashuba
Christy S
CS
Scott
Andrea
A
Gaedigk
Gregory L
GL
Kearns
D001191:Arylamine N-Acetyltransferase / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D003550:Cystic Fibrosis / Q000201:enzymology* / Q000652:urine; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism* / Q000652:urine; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D014969:Xanthine Oxidase / Q000378:metabolism* / Q000652:urine
D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase