Lack of Influence by CYP3A4 and CYP3A5 Genotypes on Pain Relief by Hydrocodone in Postoperative Cesarean Section Pain Management
| Autor: | Saeed A. Jortani, Jeremy Gaskins, Tyler Yin, Keivan Hosseinnejad, Loralie L Langman, M. Elaine Stauble, Yanhong Wu, Paul J. Jannetto |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Population 030226 pharmacology & pharmacy 01 natural sciences Biomarkers Pharmacological 03 medical and health sciences 0302 clinical medicine Statistical significance Internal medicine Cytochrome P-450 CYP3A Humans Hydromorphone Pain Management Medicine Hydrocodone education Pain Postoperative education.field_of_study Polymorphism Genetic Dose-Response Relationship Drug Cesarean Section business.industry 010401 analytical chemistry Norhydrocodone General Medicine Dihydrocodeine Pharmacogenomic Testing 0104 chemical sciences Analgesics Opioid Cytochrome P-450 CYP2D6 Opioid Cohort Female business medicine.drug |
| Zdroj: | The Journal of Applied Laboratory Medicine. 3:954-964 |
| ISSN: | 2475-7241 2576-9456 |
| Popis: | Background Genetic polymorphisms of cytochrome P450 are contributors to variability in individual response to drugs. Within the P450 family, CYP2D6 is responsible for metabolizing hydrocodone, a widely prescribed opioid for pain management. Alternatively, CYP3A4 and CYP3A5 can form norhydrocodone and dihydrocodeine. We have previously found that in a postcesarean section cohort, the rate of hydromorphone formation was dependent on the genotype of CYP2D6 and that plasma hydromorphone, not hydrocodone, was predictive of pain relief. Method Blood was obtained from a postcesarean cohort that were surveyed for pain response and common side effects. Plasma samples were genotyped for CYP3A4/5, and their hydrocodone concentrations were measured by LC-MS. R statistical software was used to check for differences in the outcomes due to CYP3A4/5 and CYP2D6, and a multivariate regression model was fit to determine factors associated with pain score. Results Two-way ANOVA between CYP3A4/A5 and CYP2D6 phenotypes revealed that the former variants did not have a statistical significance on the outcomes, and only CYP2D6 phenotypes had a significant effect on total dosage (P = 0.041). Furthermore, a 3-way ANOVA analysis showed that CYP2D6 (P = 0.036) had a predictive effect on plasma hydromorphone concentrations, and CYP3A4/A5 did not have any effect on the measured outcomes. Conclusions With respect to total dosages in a cesarean section population, these results confirm that CYP2D6 phenotypes are predictors for plasma hydromorphone concentration and pain relief, but CYP3A4/A5 phenotypes have no influence on pain relief or on side effects. |
| Databáze: | OpenAIRE |
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