{"title":"兰索拉唑在鲁氏-Y 胃旁路手术后的病态肥胖患者中的药代动力学特征","authors":"Suthep Udomsawaengsup, Sathienrapong Chantawibul, Naranon Boonyuen, Sarunnuch Panyavorakhunchai, Pattharasai Kachornvitaya, Wasu Wisanuyothin, Pittawat Somvanapanich, Warittha Lertwatthiphong, Napatsanan Tanathitiphuwarat, Pajaree Chariyavilaskul","doi":"10.1111/cts.70200","DOIUrl":null,"url":null,"abstract":"<p>Data on the effects of Roux-en-Y gastric bypass (RYGB) surgery on lansoprazole pharmacokinetics in morbidly obese patients are limited. This study aimed to evaluate the impact of RYGB surgery on the pharmacokinetic profile of lansoprazole in Thai morbidly obese patients. Participants received 30 mg of lansoprazole twice daily for 7 days before surgery and continued the regimen for 6 weeks post-surgery. Plasma lansoprazole concentrations were measured at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h after dosing, both pre- and post-surgery, using a validated high-performance liquid chromatography technique. <i>CYP2C19</i> genotyping classified participants as normal metabolizers (<i>*1</i>/<i>*1</i>) or intermediate metabolizers (<i>*1</i>/<i>*2</i> and <i>*1</i>/<i>*3</i>). Pharmacokinetic parameters, including the area under the plasma concentration-time curve from 0 to 8 h (AUC<sub>0–8 h</sub>), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax), were compared before and after surgery. A total of 13 patients (mean age 37.0 ± 3.9 years; body mass index 54.0 ± 4.8 kg/m<sup>2</sup>) were enrolled. Post-surgery, AUC<sub>0–8 h</sub> and Cmax decreased by 16% (<i>p</i> = 0.009) and 31% (<i>p</i> = 0.003), respectively, while Tmax remained unchanged. A 30% reduction in Cmax (<i>p</i> = 0.007) was observed in <i>CYP2C19</i> normal metabolizers, whereas no significant changes were noted in intermediate metabolizers. In conclusion, RYGB surgery significantly reduced lansoprazole systemic exposure, particularly in <i>CYP2C19</i> normal metabolizers. Further studies are needed to explore the clinical implications of these pharmacokinetic changes and develop optimized treatment strategies for post-RYGB patients.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: TCTR20220118001</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70200","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic Profiles of Lansoprazole in Patients With Morbid Obesity Post-Roux-en-Y Gastric Bypass Surgery\",\"authors\":\"Suthep Udomsawaengsup, Sathienrapong Chantawibul, Naranon Boonyuen, Sarunnuch Panyavorakhunchai, Pattharasai Kachornvitaya, Wasu Wisanuyothin, Pittawat Somvanapanich, Warittha Lertwatthiphong, Napatsanan Tanathitiphuwarat, Pajaree Chariyavilaskul\",\"doi\":\"10.1111/cts.70200\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Data on the effects of Roux-en-Y gastric bypass (RYGB) surgery on lansoprazole pharmacokinetics in morbidly obese patients are limited. This study aimed to evaluate the impact of RYGB surgery on the pharmacokinetic profile of lansoprazole in Thai morbidly obese patients. Participants received 30 mg of lansoprazole twice daily for 7 days before surgery and continued the regimen for 6 weeks post-surgery. Plasma lansoprazole concentrations were measured at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h after dosing, both pre- and post-surgery, using a validated high-performance liquid chromatography technique. <i>CYP2C19</i> genotyping classified participants as normal metabolizers (<i>*1</i>/<i>*1</i>) or intermediate metabolizers (<i>*1</i>/<i>*2</i> and <i>*1</i>/<i>*3</i>). Pharmacokinetic parameters, including the area under the plasma concentration-time curve from 0 to 8 h (AUC<sub>0–8 h</sub>), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax), were compared before and after surgery. A total of 13 patients (mean age 37.0 ± 3.9 years; body mass index 54.0 ± 4.8 kg/m<sup>2</sup>) were enrolled. Post-surgery, AUC<sub>0–8 h</sub> and Cmax decreased by 16% (<i>p</i> = 0.009) and 31% (<i>p</i> = 0.003), respectively, while Tmax remained unchanged. A 30% reduction in Cmax (<i>p</i> = 0.007) was observed in <i>CYP2C19</i> normal metabolizers, whereas no significant changes were noted in intermediate metabolizers. In conclusion, RYGB surgery significantly reduced lansoprazole systemic exposure, particularly in <i>CYP2C19</i> normal metabolizers. Further studies are needed to explore the clinical implications of these pharmacokinetic changes and develop optimized treatment strategies for post-RYGB patients.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: TCTR20220118001</p>\",\"PeriodicalId\":50610,\"journal\":{\"name\":\"Cts-Clinical and Translational Science\",\"volume\":\"18 3\",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70200\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cts-Clinical and Translational Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cts.70200\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cts-Clinical and Translational Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cts.70200","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Pharmacokinetic Profiles of Lansoprazole in Patients With Morbid Obesity Post-Roux-en-Y Gastric Bypass Surgery
Data on the effects of Roux-en-Y gastric bypass (RYGB) surgery on lansoprazole pharmacokinetics in morbidly obese patients are limited. This study aimed to evaluate the impact of RYGB surgery on the pharmacokinetic profile of lansoprazole in Thai morbidly obese patients. Participants received 30 mg of lansoprazole twice daily for 7 days before surgery and continued the regimen for 6 weeks post-surgery. Plasma lansoprazole concentrations were measured at predose (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h after dosing, both pre- and post-surgery, using a validated high-performance liquid chromatography technique. CYP2C19 genotyping classified participants as normal metabolizers (*1/*1) or intermediate metabolizers (*1/*2 and *1/*3). Pharmacokinetic parameters, including the area under the plasma concentration-time curve from 0 to 8 h (AUC0–8 h), maximum plasma concentration (Cmax), and time to maximum concentration (Tmax), were compared before and after surgery. A total of 13 patients (mean age 37.0 ± 3.9 years; body mass index 54.0 ± 4.8 kg/m2) were enrolled. Post-surgery, AUC0–8 h and Cmax decreased by 16% (p = 0.009) and 31% (p = 0.003), respectively, while Tmax remained unchanged. A 30% reduction in Cmax (p = 0.007) was observed in CYP2C19 normal metabolizers, whereas no significant changes were noted in intermediate metabolizers. In conclusion, RYGB surgery significantly reduced lansoprazole systemic exposure, particularly in CYP2C19 normal metabolizers. Further studies are needed to explore the clinical implications of these pharmacokinetic changes and develop optimized treatment strategies for post-RYGB patients.
期刊介绍:
Clinical and Translational Science (CTS), an official journal of the American Society for Clinical Pharmacology and Therapeutics, highlights original translational medicine research that helps bridge laboratory discoveries with the diagnosis and treatment of human disease. Translational medicine is a multi-faceted discipline with a focus on translational therapeutics. In a broad sense, translational medicine bridges across the discovery, development, regulation, and utilization spectrum. Research may appear as Full Articles, Brief Reports, Commentaries, Phase Forwards (clinical trials), Reviews, or Tutorials. CTS also includes invited didactic content that covers the connections between clinical pharmacology and translational medicine. Best-in-class methodologies and best practices are also welcomed as Tutorials. These additional features provide context for research articles and facilitate understanding for a wide array of individuals interested in clinical and translational science. CTS welcomes high quality, scientifically sound, original manuscripts focused on clinical pharmacology and translational science, including animal, in vitro, in silico, and clinical studies supporting the breadth of drug discovery, development, regulation and clinical use of both traditional drugs and innovative modalities.