{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:53:58Z","timestamp":1778626438197,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1373\/jalm.2018.026070","type":"journal-article","created":{"date-parts":[[2018,9,6]],"date-time":"2018-09-06T13:37:16Z","timestamp":1536241036000},"page":"954-964","source":"Crossref","is-referenced-by-count":4,"title":["Lack of Influence by CYP3A4 and CYP3A5 Genotypes on Pain Relief by Hydrocodone in Postoperative Cesarean Section Pain Management"],"prefix":"10.1093","volume":"3","author":[{"given":"Keivan","family":"Hosseinnejad","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Louisville, Louisville, KY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louisville, Louisville, KY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy T","family":"Gaskins","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Elaine","family":"Stauble","sequence":"additional","affiliation":[{"name":"Department of General Obstetrics, Gynecology, and Women's Health, University of Louisville, Louisville, KY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Jannetto","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loralie L","family":"Langman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed A","family":"Jortani","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louisville, Louisville, KY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"2022020118541752700_B1","unstructured":"Hughes \u00a0A, Williams \u00a0MR, Lipari \u00a0RN, Bose \u00a0J, Copello \u00a0EAP, Kroutil \u00a0LA. 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