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CYP2D6, N-acetylation, and xanthine oxidase activity in cystic fibrosis
1Department of Pharmaceutical Sciences, Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston 29425-0810, USA.
Study Objective:
To determine the activity of CYP2D6, N-acetylation, and xanthine oxidase, three drug-metabolizing enzyme systems, in patients with cystic fibrosis and compare the findings with those in individuals without the disease.
Design:
Prospective cohort study.
Setting:
General pediatrics service.
Patients:
Fifty-nine patients with cystic fibrosis and 480 healthy Caucasian volunteers.
Interventions:
Enzyme activity was determined based on urinary molar metabolite ratios of caffeine and dextromethorphan probes.
Measurements And Main Results:
The percentage of poor metabolizers of CYP2D6 in patients with cystic fibrosis was not different from that in the control group (p = 0.45). N-Acetylation activity was significantly lower in the patients (p = 0.007), but no statistically significant difference was found in xanthine oxidase activity (p = 0.12).
Conclusion:
The activity of these drug-metabolic pathways does not appear to be increased in cystic fibrosis. Whether the activity of other pathways is increased, thus providing a partial explanation for the generally increased drug clearance in this disease, remains to be determined.
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