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

Pål Sandvik1, Stian Lydersen2, Solfrid Hegstad3

  • 1Department of Psychiatry, St. Olav University Hospital, Trondheim, Norway.

Pharmacology Research & Perspectives
|June 13, 2020
PubMed

Insights

Severe underweight impacts drug metabolism. This study found that increasing body mass index (BMI) in anorexia nervosa patients decreased CYP3A4 activity and, with borderline significance, increased CYP1A2 activity, affecting drug processing.

Area of Science:

  • Pharmacology
  • Clinical Nutrition
  • Biochemistry

Background:

  • Limited understanding of how severe underweight affects cytochrome P-450 (CYP) enzyme activity.
  • Anorexia nervosa patients exhibit significant physiological changes impacting drug metabolism.

Purpose of the Study:

  • To investigate the relationship between body mass index (BMI) and the activity of key CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) in patients with anorexia nervosa.
  • To quantify the impact of BMI changes on the metabolic activity of these enzymes.

Main Methods:

  • A cohort of 24 anorexia nervosa patients ingested single oral doses of five CYP substrate drugs.
  • Mixed-model analysis was employed to assess the correlation between BMI changes and drug/metabolite ratios.
  • Primary endpoint: change in drug/metabolite ratio per kg/m² change in BMI.

Main Results:

  • Increased BMI was associated with decreased CYP3A4 metabolic activity (P=0.017).
  • Increased BMI showed a borderline significant trend towards increased CYP1A2 activity (P=0.059).
  • No significant changes in CYP2C9, CYP2C19, or CYP2D6 activity were observed with BMI changes.

Conclusions:

  • Severe underweight, as seen in anorexia nervosa, significantly alters CYP3A4 and potentially CYP1A2 enzyme activity.
  • Further research into drug pharmacokinetics in underweight populations is crucial, especially for drugs metabolized by CYP1A2 and CYP3A4.
Keywords:
anorexia nervosabody weightcytochrome P-450drug treatment

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