Does cytochrome 2D6 genotype affect the analgesic efficacy of codeine after ambulatory surgery? Prospective trial in 987 adults
Article Swipe
Satu Poikola
,
Hanna von Plato
,
Jukka Harju
,
Johanna I. Kiiski
,
Kristiina Mattila
,
Klaus T. Olkkola
,
Mikko Niemi
,
Eija Kalso
,
Vesa K. Kontinen
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1111/aas.14549
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1111/aas.14549
Background Paracetamol–codeine combination tablet is widely used in pain management after day surgery. For safety reasons, its use has decreased in recent years. Codeine is a prodrug metabolised in the liver by the cytochrome P450 2D6 (CYP2D6) enzyme to morphine that produces the analgesic effect of codeine. CYP2D6 is highly polymorphic, and based on genotypes, individuals can be divided into four categories: poor‐, intermediate‐, normal‐ and ultrarapid metabolisers. Differences in morphine and its metabolite concentrations have been described between different CYP2D6 genotypes following codeine administration. The aim of the study was to investigate the possible effect of CYP2D6 genotype on codeine efficacy and adverse effects in a large cohort of adult patients undergoing ambulatory surgery. Methods A total of 987 patients scheduled for ambulatory surgery were included in the analyses. Operation types or anaesthesia methods were not limited in the study protocol. All study patients received a fixed dose of paracetamol (1000 mg) and codeine (60 mg) orally for premedication. A blood sample was drawn to identify the genotype of CYP2D6. At home, the first‐line analgesic was paracetamol–codeine combination of 1–2 tablets at 1–3 times per day. Data on the efficacy and side effects of codeine were collected on the day of surgery and the following two postoperative days. Results Of the studied patients, 37 (3.7%) were poor CYP2D6 metabolisers, 264 (27%) were intermediate, 623 (63%) were normal and 63 (6.4%) were ultrarapid metabolisers. Activity scores ranged from 0 to 4. CYP2D6 genotype was not associated in a statistically significant manner with postoperative pain, opioid consumption or the adverse effects of codeine, except for constipation at home. Poor CYP2D6 metabolisers reported significantly less severe constipation compared with normal metabolisers ( p = .009, OR 0.40, 95% Cl 0.20–0.80). Conclusion CYP2D6 genotype appears to be of minor importance for the analgesic efficacy of oral paracetamol‐codeine combination therapy after ambulatory surgery in adult patients undergoing similar types of surgery as in the present study but it may affect the risk of constipation.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/aas.14549
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aas.14549
- OA Status
- hybrid
- References
- 25
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4404355961
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4404355961Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/aas.14549Digital Object Identifier
- Title
-
Does cytochrome
2D6 genotype affect the analgesic efficacy of codeine after ambulatory surgery? Prospective trial in 987 adultsWork title - Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-11-14Full publication date if available
- Authors
-
Satu Poikola, Hanna von Plato, Jukka Harju, Johanna I. Kiiski, Kristiina Mattila, Klaus T. Olkkola, Mikko Niemi, Eija Kalso, Vesa K. KontinenList of authors in order
- Landing page
-
https://doi.org/10.1111/aas.14549Publisher landing page
- PDF URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aas.14549Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aas.14549Direct OA link when available
- Concepts
-
Codeine, Medicine, Analgesic, Morphine, CYP2D6, Anesthesia, Ambulatory, Adverse effect, Pharmacology, Randomized controlled trial, Internal medicine, Cytochrome P450, MetabolismTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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25Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index..009, | 283 |
| abstract_inverted_index.0.40, | 285 |
| abstract_inverted_index.1–2 | 181 |
| abstract_inverted_index.1–3 | 184 |
| abstract_inverted_index.adult | 111, 311 |
| abstract_inverted_index.after | 11, 307 |
| abstract_inverted_index.based | 53 |
| abstract_inverted_index.blood | 162 |
| abstract_inverted_index.days. | 209 |
| abstract_inverted_index.drawn | 165 |
| abstract_inverted_index.fixed | 148 |
| abstract_inverted_index.home, | 173 |
| abstract_inverted_index.home. | 267 |
| abstract_inverted_index.large | 108 |
| abstract_inverted_index.liver | 31 |
| abstract_inverted_index.minor | 296 |
| abstract_inverted_index.pain, | 254 |
| abstract_inverted_index.study | 90, 141, 144, 322 |
| abstract_inverted_index.times | 185 |
| abstract_inverted_index.total | 118 |
| abstract_inverted_index.types | 132, 315 |
| abstract_inverted_index.(3.7%) | 216 |
| abstract_inverted_index.(6.4%) | 231 |
| abstract_inverted_index.CYP2D6 | 48, 81, 98, 219, 242, 269, 290 |
| abstract_inverted_index.affect | 326 |
| abstract_inverted_index.cohort | 109 |
| abstract_inverted_index.effect | 45, 96 |
| abstract_inverted_index.enzyme | 38 |
| abstract_inverted_index.except | 263 |
| abstract_inverted_index.highly | 50 |
| abstract_inverted_index.manner | 251 |
| abstract_inverted_index.normal | 228, 278 |
| abstract_inverted_index.opioid | 255 |
| abstract_inverted_index.orally | 158 |
| abstract_inverted_index.ranged | 237 |
| abstract_inverted_index.recent | 22 |
| abstract_inverted_index.safety | 15 |
| abstract_inverted_index.sample | 163 |
| abstract_inverted_index.scores | 236 |
| abstract_inverted_index.severe | 274 |
| abstract_inverted_index.tablet | 4 |
| abstract_inverted_index.widely | 6 |
| abstract_inverted_index.years. | 23 |
| abstract_inverted_index.CYP2D6. | 171 |
| abstract_inverted_index.Codeine | 24 |
| abstract_inverted_index.Methods | 116 |
| abstract_inverted_index.Results | 210 |
| abstract_inverted_index.adverse | 104, 259 |
| abstract_inverted_index.appears | 292 |
| abstract_inverted_index.between | 79 |
| abstract_inverted_index.codeine | 84, 101, 155, 196 |
| abstract_inverted_index.divided | 59 |
| abstract_inverted_index.effects | 105, 194, 260 |
| abstract_inverted_index.limited | 138 |
| abstract_inverted_index.methods | 135 |
| abstract_inverted_index.present | 321 |
| abstract_inverted_index.prodrug | 27 |
| abstract_inverted_index.similar | 314 |
| abstract_inverted_index.studied | 213 |
| abstract_inverted_index.surgery | 125, 203, 309, 317 |
| abstract_inverted_index.tablets | 182 |
| abstract_inverted_index.therapy | 306 |
| abstract_inverted_index.(CYP2D6) | 37 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.Activity | 235 |
| abstract_inverted_index.codeine, | 262 |
| abstract_inverted_index.codeine. | 47 |
| abstract_inverted_index.compared | 276 |
| abstract_inverted_index.efficacy | 102, 191, 301 |
| abstract_inverted_index.genotype | 99, 169, 243, 291 |
| abstract_inverted_index.identify | 167 |
| abstract_inverted_index.included | 127 |
| abstract_inverted_index.morphine | 40, 71 |
| abstract_inverted_index.patients | 112, 121, 145, 312 |
| abstract_inverted_index.poor‐, | 63 |
| abstract_inverted_index.possible | 95 |
| abstract_inverted_index.produces | 42 |
| abstract_inverted_index.reasons, | 16 |
| abstract_inverted_index.received | 146 |
| abstract_inverted_index.reported | 271 |
| abstract_inverted_index.surgery. | 13, 115 |
| abstract_inverted_index.Operation | 131 |
| abstract_inverted_index.analgesic | 44, 176, 300 |
| abstract_inverted_index.analyses. | 130 |
| abstract_inverted_index.collected | 198 |
| abstract_inverted_index.decreased | 20 |
| abstract_inverted_index.described | 78 |
| abstract_inverted_index.different | 80 |
| abstract_inverted_index.following | 83, 206 |
| abstract_inverted_index.genotypes | 82 |
| abstract_inverted_index.normal‐ | 65 |
| abstract_inverted_index.patients, | 214 |
| abstract_inverted_index.protocol. | 142 |
| abstract_inverted_index.scheduled | 122 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.Conclusion | 289 |
| abstract_inverted_index.ambulatory | 114, 124, 308 |
| abstract_inverted_index.associated | 246 |
| abstract_inverted_index.cytochrome | 34 |
| abstract_inverted_index.genotypes, | 55 |
| abstract_inverted_index.importance | 297 |
| abstract_inverted_index.management | 10 |
| abstract_inverted_index.metabolite | 74 |
| abstract_inverted_index.ultrarapid | 67, 233 |
| abstract_inverted_index.undergoing | 113, 313 |
| abstract_inverted_index.Differences | 69 |
| abstract_inverted_index.anaesthesia | 134 |
| abstract_inverted_index.categories: | 62 |
| abstract_inverted_index.combination | 3, 179, 305 |
| abstract_inverted_index.consumption | 256 |
| abstract_inverted_index.individuals | 56 |
| abstract_inverted_index.investigate | 93 |
| abstract_inverted_index.metabolised | 28 |
| abstract_inverted_index.paracetamol | 151 |
| abstract_inverted_index.significant | 250 |
| abstract_inverted_index.constipation | 265, 275 |
| abstract_inverted_index.first‐line | 175 |
| abstract_inverted_index.metabolisers | 270, 279 |
| abstract_inverted_index.polymorphic, | 51 |
| abstract_inverted_index.0.20–0.80). | 288 |
| abstract_inverted_index.constipation. | 330 |
| abstract_inverted_index.intermediate, | 224 |
| abstract_inverted_index.metabolisers, | 220 |
| abstract_inverted_index.metabolisers. | 68, 234 |
| abstract_inverted_index.postoperative | 208, 253 |
| abstract_inverted_index.significantly | 272 |
| abstract_inverted_index.statistically | 249 |
| abstract_inverted_index.concentrations | 75 |
| abstract_inverted_index.premedication. | 160 |
| abstract_inverted_index.administration. | 85 |
| abstract_inverted_index.intermediate‐, | 64 |
| abstract_inverted_index.Paracetamol–codeine | 2 |
| abstract_inverted_index.paracetamol‐codeine | 304 |
| abstract_inverted_index.paracetamol–codeine | 178 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5007640654 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I133731052, https://openalex.org/I2800394112 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.4099999964237213 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.42680245 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |