CYP2D6, N‐Acetylation, and Xanthine Oxidase Activity in Cystic Fibrosis

Abstract

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.