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CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice.

ABSTRACT: Cytochrome P450 2D6 (CYP2D6) O-demethylates codeine to the active drug, morphine. However, the utility of testing for CYP2D6 metabolizer status in patients receiving codeine in real-world clinical practice is poorly defined. Using data from a DNA bank linked to de-identified electronic health records, we studied 157 patients with a baseline pain score higher than 4 (0-10 scale) who received codeine. Based on CYP2D6 genotyping, 69 were classified as poor/intermediate and 88 as normal/ultrarapid CYP2D6 metabolizers. Pain response was defined as a score of 4 or lower while receiving codeine. In a propensity-score adjusted model, poor/intermediate metabolizers had lower odds (OR = 0.35, p = 0.02) of achieving a pain response than normal/ultrarapid metabolizers. To discriminate between codeine responders and nonresponders, a score including CYP2D6 phenotype and clinical variables was built. The response rate was 38.5% among patients in the high, 17.3% in the intermediate, and 9.4% in the low-score groups, respectively (p = 0.001).

SUBMITTER: Carranza-Leon D

PROVIDER: S-EPMC8295171 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice.

Carranza-Leon Daniel D Dickson Alyson L AL Gaedigk Andrea A Stein C Michael CM Chung Cecilia P CP

The pharmacogenomics journal 20210309 4

Cytochrome P450 2D6 (CYP2D6) O-demethylates codeine to the active drug, morphine. However, the utility of testing for CYP2D6 metabolizer status in patients receiving codeine in real-world clinical practice is poorly defined. Using data from a DNA bank linked to de-identified electronic health records, we studied 157 patients with a baseline pain score higher than 4 (0-10 scale) who received codeine. Based on CYP2D6 genotyping, 69 were classified as poor/intermediate and 88 as normal/ultrarapid C ...[more]

PMID: 33750887

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Project description:IntroductionIn this literature review we evaluated the real-world clinical effectiveness of switching Japanese diabetic patients from their current insulin regimen to insulin degludec (IDeg).MethodsStudies were identified from Japanese Diabetes Society (JDS) abstracts (2014-2015) and PubMed (2012 onwards). Inclusion criteria were: Japanese population, >15 participants, and studies switching patients from basal or basal-bolus insulin regimens to IDeg. Randomized controlled trials and case reports were excluded. Weighted mean changes in safety and effectiveness endpoints were calculated using the number of patients in each study.ResultsIn total, 81 JDS abstracts and seven manuscripts met the search criteria, representing 4238 patients [1028 with type 1 diabetes (T1D), 602 with type 2 diabetes (T2D), 2608 with unspecified or mixed diabetes]. Glycated hemoglobin (HbA1c) was reported in 93% of studies, with an improvement in 84% of these (51% significant, 33% numerical), no change in 12%, and worsening in 4% (3% numerical, 1% significant). Across all studies, the weighted mean absolute change in HbA1c was -0.3% (-2.7 mmol/mol). Basal insulin dose was reported in 58% of studies and was lower in 60% of these (30% significant, 30% numerical), numerically unchanged in 26%, and higher in 14% (2% significant, 12% numerical). The weighted mean change in basal insulin dose was -4.8% and -3.0% for all studies and for studies with only significant results, respectively. The weighted mean change in basal dose based on all studies was -8.9, -5.5, and -2.9% for the T1D, T2D, and unspecified patient populations, respectively. Hypoglycemia was recorded in 31% of the studies. After switching treatment to IDeg, 55% of studies reported decreased hypoglycemia, 29% no change, and 16% an increase. Quality of life (QoL) was measured in 11% of studies, of which 82% reported improved QoL after switching, and 18% reported no change in QoL.ConclusionSwitching from a conventional basal insulin to IDeg has the potential to improve HbA1c with a lower insulin dose. Switching to IDeg may also provide a reduced risk of hypoglycemia and improvement in QoL.FundingNovo Nordisk.

Dataset Information

CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice.

Publications

CYP2D6 genotype and reduced codeine analgesic effect in real-world clinical practice.

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