Correlation of Body Weight and Composition With Hepatic Activities of Cytochrome P450 Enzymes
| Autor: | Tommy B. Andersson, Hege Christensen, Philip Carlo Angeles, Veronica Krogstad, Shalini Andersson, Anders Åsberg, Line Kristin Johnson, Maria Vistnes, Rune Sandbu, Cecilia Karlsson, Jøran Hjelmesæth, Marianne Kristiansen Kringen, Ida Robertsen, Alexandra Peric, Rasmus Jansson-Löfmark |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
CYP2B6 CYP3A Pharmaceutical Science Cytochrome P450 02 engineering and technology 030226 pharmacology & pharmacy 03 medical and health sciences First pass effect 0302 clinical medicine Cytochrome P-450 Enzyme System Pharmacokinetics Internal medicine Human liver microsomes Cytochrome P-450 CYP3A Humans Medicine CYP2C8 Cytochrome P-450 CYP2C9 business.industry Body Weight CYP1A2 021001 nanoscience & nanotechnology First pass metabolisms Drug metabolizing enzymes Hepatic metabolisms Endocrinology Cytochrome P-450 CYP2D6 Liver Microsomes Liver Phase 1 metabolisms 0210 nano-technology business Body mass index Drug metabolism |
| Zdroj: | Journal of Pharmaceutical Sciences |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2020.10.027 |
| Popis: | Obesity is associated with comorbidities of which pharmacological treatment is needed. Physiological changes associated with obesity may influence the pharmacokinetics of drugs, but the effect of body weight on drug metabolism capacity remains uncertain. The aim of this study was to investigate ex vivo activities of hepatic drug metabolizing CYP enzymes in patients covering a wide range of body weight. Liver biopsies from 36 individuals with a body mass index (BMI) ranging from 18 to 63 kg/m2 were obtained. Individual hepatic microsomes were prepared and activities of CYP3A, CYP2B6, CYP2C8, CYP2D6, CYP2C9, CYP2C19 and CYP1A2 were determined. The unbound intrinsic clearance (CLint,u) values for CYP3A correlated negatively with body weight (r = −0.43, p < 0.01), waist circumference (r = −0.47, p < 0.01), hip circumference (r = −0.51, p < 0.01), fat percent (r = −0.41, p < 0.05), fat mass (r = −0.48, p < 0.01) and BMI (r = −0.46, p < 0.01). Linear regression analysis showed that CLint,u values for CYP3A decreased with 5% with each 10% increase in body weight (r2 = 0.12, β = −0.558, p < 0.05). There were no correlations between body weight measures and CLint,u values for the other CYP enzymes investigated. These results indicate reduced hepatic metabolizing capacity of CYP3A substrates in patients with increasing body weight. |
| Databáze: | OpenAIRE |
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