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减重手术的药代动力学效应。

Pharmacokinetic effects of bariatric surgery.

机构信息

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.

出版信息

Ann Pharmacother. 2012 Jan;46(1):130-6. doi: 10.1345/aph.1Q414. Epub 2011 Dec 20.

Abstract

OBJECTIVE

To evaluate the effect of bariatric surgery on the pharmacokinetics of medications.

DATA SOURCES

EMBASE (1980-September 2011), PubMed (1947-September 2011), MEDLINE (1948-September 2011), and International Pharmaceutical Abstracts (1970-September 2011) were searched for the following terms: gastric bypass or stomach bypass or bariatric surgery, and pharmacokinetic.

STUDY SELECTION AND DATA EXTRACTION

All English-language primary literature that reported pharmacokinetic parameters for orally dosed medications in post-bariatric surgery patients was evaluated, with the exception of studies involving the jejunoileal bypass method.

DATA SYNTHESIS

Worldwide, the incidence of obesity is increasing and so are options for managing it, including bariatric surgery. Major alterations to the physical structure of the gastrointestinal tract may cause changes in pharmacokinetic parameters of oral medications, which theoretically could lead to increased or decreased drug exposure. We reviewed 11 prospective trials, 5 of which were available only as abstracts and all of which were small with relatively low power (n = 6-36). The studies were split almost equally between using subjects as their own controls or using separate control subjects; 1 study used historical data as the control. Results were varied, highlighting the multifactorial nature of pharmacokinetics. Drugs such as atorvastatin, which undergo presystemic intestinal metabolism via CYP3A, may show increased bioavailability, whereas those such as amoxicillin, which rely on transport mediators, may be decreased. Most of the studies lacked sufficient power to show significant changes in post-bariatric surgery patients.

CONCLUSIONS

Bariatric surgical procedures may result in altered pharmacokinetic parameters, but the literature is lacking in sufficient quantity and quality of studies to make solid conclusions and recommendations. Until more studies of sufficient power are completed, clinicians should closely monitor these patients in the immediate and distant postsurgical period for signs of both drug efficacy and toxicity and adjust their medications as required.

摘要

目的

评估减重手术对药物药代动力学的影响。

资料来源

EMBASE(1980 年-2011 年 9 月)、PubMed(1947 年-2011 年 9 月)、MEDLINE(1948 年-2011 年 9 月)和国际药学文摘(1970 年-2011 年 9 月)搜索了以下术语:胃旁路或胃旁路或减重手术和药代动力学。

研究选择和数据提取

评估了所有报告术后减重手术患者口服药物药代动力学参数的英文原始文献,除了涉及空肠回肠旁路方法的研究外。

数据综合

全世界肥胖症的发病率正在上升,治疗方法也在增加,包括减重手术。胃肠道物理结构的重大改变可能导致口服药物药代动力学参数的变化,这从理论上讲可能导致药物暴露增加或减少。我们回顾了 11 项前瞻性试验,其中 5 项仅作为摘要提供,所有试验都很小,相对功率较低(n = 6-36)。这些研究几乎平分使用患者自身作为对照或使用单独的对照;1 项研究使用历史数据作为对照。结果各不相同,突出了药代动力学的多因素性质。如阿托伐他汀,其通过 CYP3A 进行肠前代谢的药物,可能显示生物利用度增加,而那些如阿莫西林,其依赖转运介质的药物,可能会减少。大多数研究缺乏足够的能力来显示减重手术后患者的显著变化。

结论

减重手术可能导致药代动力学参数改变,但文献缺乏足够数量和质量的研究来做出明确的结论和建议。在完成更多足够数量和质量的研究之前,临床医生应在手术的近期和远期密切监测这些患者的药物疗效和毒性迹象,并根据需要调整药物剂量。

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