著者
Takaki Kamiya Daiki Hira Ryo Nakajima Kazuha Shinoda Atsuko Motomochi Aya Morikochi Yoshito Ikeda Tetsuichiro Isono Michiya Akabane Satoshi Ueshima Mikio Kakumoto Shinji Imai Shin-ya Morita Tomohiro Terada
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.46, no.7, pp.907-913, 2023-07-01 (Released:2023-07-01)
参考文献数
31
被引用文献数
1

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.
著者
Yuichi Sawayama Takashi Yamamoto Yukinori Tomita Kohei Asada Noriaki Yagi Megumi Fukuyama Akashi Miyamoto Hiroshi Sakai Tomoya Ozawa Tetsuichiro Isono Daiki Hira Tomohiro Terada Minoru Horie Yoshihisa Nakagawa
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.84, no.9, pp.1575-1581, 2020-08-25 (Released:2020-08-25)
参考文献数
18
被引用文献数
5 13

Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.