Abstract
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/m2 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 part...Continue Reading
References
Jan 1, 1995·International Archives of Occupational and Environmental Health·P N Lee
Nov 26, 1999·Life Sciences·G L HendersonD M Stresser
Sep 8, 2000·Clinical Pharmacology and Therapeutics·K LaineL Bertilsson
Mar 22, 2001·British Journal of Clinical Pharmacology·S HäggR Dahlqvist
Jun 18, 2003·Clinical Pharmacology and Therapeutics·Magnus ChristensenLeif Bertilsson
Aug 5, 2003·British Journal of Clinical Pharmacology·Sanna PalovaaraKari Laine
Jan 17, 2007·Journal of Clinical Psychopharmacology·Sheldon H PreskornTal Burt
Mar 30, 2007·Clinical Pharmacology and Therapeutics·J Y RyuJ G Shin
Mar 1, 2012·Frontiers in Pharmacology·Hege Christensen, Monica Hermann
Mar 28, 2012·Clinical Pharmacokinetics·Margreke J E BrillCatherijne A J Knibbe
Jan 22, 2013·Pharmacology & Therapeutics·Ulrich M Zanger, Matthias Schwab
Jan 31, 2013·Clinical Pharmacology and Therapeutics·M UlvestadH Christensen
Feb 14, 2014·Drug Metabolism and Pharmacokinetics·Linda Björkhem-BergmanUlf Diczfalusy
Dec 3, 2014·Psychoneuroendocrinology·Marco SolmiChristoph U Correll
Apr 22, 2015·Steroids·Marie Tremblay-FrancoLuigi Iuliano
Sep 25, 2015·Basic & Clinical Pharmacology & Toxicology·Sarah J WoolseyRommel G Tirona
Nov 29, 2015·European Journal of Clinical Pharmacology·Ole Kristian ThuBent Hellum
Apr 16, 2016·Clinical Pharmacology and Therapeutics·Yasar TasnifMary F Hebert
Oct 21, 2016·Clinical Pharmacokinetics·Gail D Anderson, Lingtak-Neander Chan
Aug 22, 2018·Endocrine, Metabolic & Immune Disorders Drug Targets·Mina RabieeMohammad Mojerloo
Sep 15, 2018·Pharmacology Research & Perspectives·Kristine HoleEspen Molden
Citations
Nov 4, 2020·European Journal of Nutrition·Meysam ZarezadehDaniel J Müller
Mar 30, 2021·Journal of Medical Case Reports·Kanitpong Phabphal, Prut Koonalintip
Jul 25, 2021·International Journal of Molecular Sciences·Ellen Niederberger, Michael J Parnham
Aug 20, 2021·Pharmacogenomics·Aggeliki CharalampidiMaria Koromina
Dec 18, 2021·Expert Review of Clinical Pharmacology·Georgios SchoretsanitisMichael Paulzen