Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery
Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for post...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 2023/07/01, Vol.46(7), pp.907-913 |
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| creator | Kamiya, Takaki Hira, Daiki Nakajima, Ryo Shinoda, Kazuha Motomochi, Atsuko Morikochi, Aya Ikeda, Yoshito Isono, Tetsuichiro Akabane, Michiya Ueshima, Satoshi Kakumoto, Mikio Imai, Shinji Morita, Shin-ya Terada, Tomohiro |
| description | Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017–March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann–Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p |
| doi_str_mv | 10.1248/bpb.b23-00030 |
| format | Article |
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This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017–March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann–Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p < 0.05). The multiple linear regression analysis indicated that the CYP2D6 polymorphism was a prediction factor of the high NRS-AUC levels in Days 0–7 (β = 9.52, 95% CI 1.30–17.7). In IM patients, the analgesic effect of tramadol was significantly reduced one week after orthopedic surgery in clinical practice. Therefore, dose escalation of tramadol or the use of alternative analgesic medications can be recommended for IM patients.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b23-00030</identifier><identifier>PMID: 37394642</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Analgesics ; Bone surgery ; Clinical medicine ; CYP2D6 ; CYP2D6 protein ; Cytochrome P450 ; Gene polymorphism ; Orthopedics ; Pain ; Patients ; pharmacodynamics ; Phenotypes ; polymorphism ; precision medicine ; Regression analysis ; Surgery ; Tramadol</subject><ispartof>Biological and Pharmaceutical Bulletin, 2023/07/01, Vol.46(7), pp.907-913</ispartof><rights>2023 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-4587bf7d13069a61a19e79354a49bd4de7564ef7aac21906676d395185c9e1973</citedby><cites>FETCH-LOGICAL-c554t-4587bf7d13069a61a19e79354a49bd4de7564ef7aac21906676d395185c9e1973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37394642$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kamiya, Takaki</creatorcontrib><creatorcontrib>Hira, Daiki</creatorcontrib><creatorcontrib>Nakajima, Ryo</creatorcontrib><creatorcontrib>Shinoda, Kazuha</creatorcontrib><creatorcontrib>Motomochi, Atsuko</creatorcontrib><creatorcontrib>Morikochi, Aya</creatorcontrib><creatorcontrib>Ikeda, Yoshito</creatorcontrib><creatorcontrib>Isono, Tetsuichiro</creatorcontrib><creatorcontrib>Akabane, Michiya</creatorcontrib><creatorcontrib>Ueshima, Satoshi</creatorcontrib><creatorcontrib>Kakumoto, Mikio</creatorcontrib><creatorcontrib>Imai, Shinji</creatorcontrib><creatorcontrib>Morita, Shin-ya</creatorcontrib><creatorcontrib>Terada, Tomohiro</creatorcontrib><title>Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017–March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann–Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p < 0.05). The multiple linear regression analysis indicated that the CYP2D6 polymorphism was a prediction factor of the high NRS-AUC levels in Days 0–7 (β = 9.52, 95% CI 1.30–17.7). In IM patients, the analgesic effect of tramadol was significantly reduced one week after orthopedic surgery in clinical practice. Therefore, dose escalation of tramadol or the use of alternative analgesic medications can be recommended for IM patients.</description><subject>Analgesics</subject><subject>Bone surgery</subject><subject>Clinical medicine</subject><subject>CYP2D6</subject><subject>CYP2D6 protein</subject><subject>Cytochrome P450</subject><subject>Gene polymorphism</subject><subject>Orthopedics</subject><subject>Pain</subject><subject>Patients</subject><subject>pharmacodynamics</subject><subject>Phenotypes</subject><subject>polymorphism</subject><subject>precision medicine</subject><subject>Regression analysis</subject><subject>Surgery</subject><subject>Tramadol</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpd0T1vFDEQBmALgcgRKGmRJZo0G_ztdRldAgQFJRKhoLJmvbN3e9rbPWyvUPLr8eXCFTSeYh69kucl5D1n51yo-lOza84bISvGmGQvyIJLZSstuH5JFszxujJc1yfkTUqbQiwT8jU5kVY6ZZRYkMdLDBEhYUsvRhhWmPpAr7oOQ6ZTR-8jbKGdBtqP9BvsYMSE9A5yj2NO9E-f13T5605cGno9ZoxbbHvISL9jhmYa-keMiUJXNvQ25vW0K_tAf8xxhfHhLXnVwZDw3fM8JT8_X90vv1Y3t1-ulxc3VdBa5Urp2jadbblkxoHhwB1aJ7UC5ZpWtWi1UdhZgCC4Y8ZY00qnea2DQ-6sPCVnh9xdnH7PmLLf9ingMJTfTHPyopaiVoybPf34H91Mcyx32SvNlBG2dkVVBxXilFLEzu9iv4X44Dnz-1J8KcWXUvxTKcV_eE6dm3Kho_7XQgHLA9ikDCs8Aoi5DwM-xSnj7f45xh63YQ3R4yj_Amtenwc</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Kamiya, Takaki</creator><creator>Hira, Daiki</creator><creator>Nakajima, Ryo</creator><creator>Shinoda, Kazuha</creator><creator>Motomochi, Atsuko</creator><creator>Morikochi, Aya</creator><creator>Ikeda, Yoshito</creator><creator>Isono, Tetsuichiro</creator><creator>Akabane, Michiya</creator><creator>Ueshima, Satoshi</creator><creator>Kakumoto, Mikio</creator><creator>Imai, Shinji</creator><creator>Morita, Shin-ya</creator><creator>Terada, Tomohiro</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20230701</creationdate><title>Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery</title><author>Kamiya, Takaki ; Hira, Daiki ; Nakajima, Ryo ; Shinoda, Kazuha ; Motomochi, Atsuko ; Morikochi, Aya ; Ikeda, Yoshito ; Isono, Tetsuichiro ; Akabane, Michiya ; Ueshima, Satoshi ; Kakumoto, Mikio ; Imai, Shinji ; Morita, Shin-ya ; Terada, Tomohiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c554t-4587bf7d13069a61a19e79354a49bd4de7564ef7aac21906676d395185c9e1973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analgesics</topic><topic>Bone surgery</topic><topic>Clinical medicine</topic><topic>CYP2D6</topic><topic>CYP2D6 protein</topic><topic>Cytochrome P450</topic><topic>Gene polymorphism</topic><topic>Orthopedics</topic><topic>Pain</topic><topic>Patients</topic><topic>pharmacodynamics</topic><topic>Phenotypes</topic><topic>polymorphism</topic><topic>precision medicine</topic><topic>Regression analysis</topic><topic>Surgery</topic><topic>Tramadol</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kamiya, Takaki</creatorcontrib><creatorcontrib>Hira, Daiki</creatorcontrib><creatorcontrib>Nakajima, Ryo</creatorcontrib><creatorcontrib>Shinoda, Kazuha</creatorcontrib><creatorcontrib>Motomochi, Atsuko</creatorcontrib><creatorcontrib>Morikochi, Aya</creatorcontrib><creatorcontrib>Ikeda, Yoshito</creatorcontrib><creatorcontrib>Isono, Tetsuichiro</creatorcontrib><creatorcontrib>Akabane, Michiya</creatorcontrib><creatorcontrib>Ueshima, Satoshi</creatorcontrib><creatorcontrib>Kakumoto, Mikio</creatorcontrib><creatorcontrib>Imai, Shinji</creatorcontrib><creatorcontrib>Morita, Shin-ya</creatorcontrib><creatorcontrib>Terada, Tomohiro</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kamiya, Takaki</au><au>Hira, Daiki</au><au>Nakajima, Ryo</au><au>Shinoda, Kazuha</au><au>Motomochi, Atsuko</au><au>Morikochi, Aya</au><au>Ikeda, Yoshito</au><au>Isono, Tetsuichiro</au><au>Akabane, Michiya</au><au>Ueshima, Satoshi</au><au>Kakumoto, Mikio</au><au>Imai, Shinji</au><au>Morita, Shin-ya</au><au>Terada, Tomohiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>46</volume><issue>7</issue><spage>907</spage><epage>913</epage><pages>907-913</pages><artnum>b23-00030</artnum><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017–March 2019. The impact of CYP2D6 genotypes on the analgesic effects was assessed by the numeric rating scale (NRS) pain scoring and analyzed by the Mann–Whitney U test. Stepwise multiple linear regression analysis was performed to identify predictive factors for the area under the time-NRS curve (NRS-AUC), which was calculated using the linear trapezoidal method. Among the 85 enrolled Japanese patients, the number of phenotypes with CYP2D6 normal metabolizer (NM) and intermediate metabolizer (IM) was n = 69 (81.1%) and n = 16 (18.9%), respectively. The NRS and NRS-AUC in the IM group were significantly higher than those in the NM group until Day 7 (p < 0.05). The multiple linear regression analysis indicated that the CYP2D6 polymorphism was a prediction factor of the high NRS-AUC levels in Days 0–7 (β = 9.52, 95% CI 1.30–17.7). In IM patients, the analgesic effect of tramadol was significantly reduced one week after orthopedic surgery in clinical practice. Therefore, dose escalation of tramadol or the use of alternative analgesic medications can be recommended for IM patients.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>37394642</pmid><doi>10.1248/bpb.b23-00030</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analgesics Bone surgery Clinical medicine CYP2D6 CYP2D6 protein Cytochrome P450 Gene polymorphism Orthopedics Pain Patients pharmacodynamics Phenotypes polymorphism precision medicine Regression analysis Surgery Tramadol |
| title | Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery |
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