Association between low body weight and cytochrome P-450 enzyme activity in patients with anorexia nervosa

Very little is known to which extent severe underweight could affect cytochrome P-450 (CYP) enzyme activity. In this study, 24 patients with anorexia nervosa at two occasions ingested single oral doses of five test drugs known to be metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. A mixed model analysis was used to evaluate the effect of changes in body mass index (BMI) on the metabolic activities of these enzymes. The primary end point was the change in drug/metabolite ratio of each of the test drugs per kg/m(2)change in BMI. With increasing BMI, the metabolic activity of CYP3A4 decreased (change in the CYP3A4 drug/metabolite ratio per unit change in BMI = 0.056; 95% confidence interval [CI] 0.011 to 0.102;P = .017). For CYP1A2, increasing BMI increased the metabolic activity with borderline significance (change in the CYP1A2 drug/metabolite ratio per unit change in BMI = -0.107; CI -0.220 to 0.005;P = .059). For CYP2C9, CYP2C19, and CYP2D6, no significant changes were seen. The clinical impact of these findings for drug treatment in patients with anorexia nervosa and other severely underweight patients needs to be further studied by examining the pharmacokinetics of specific drugs. This might be particularly relevant for drugs metabolized by CYP1A2 and/or CYP3A4.