CYP2D6, N-acetylation, and xanthine oxidase activity in cystic fibrosis.
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.