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不同减重手术前后的胃 pH 值:药物输送的临床意义。

Stomach pH before vs. after different bariatric surgery procedures: Clinical implications for drug delivery.

机构信息

Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.

Department of Surgery B, Soroka University Medical Center, Beer-Sheva 84101, Israel.

出版信息

Eur J Pharm Biopharm. 2021 Mar;160:152-157. doi: 10.1016/j.ejpb.2021.01.016. Epub 2021 Jan 30.

Abstract

Stomach pH may vary following bariatric surgery, with implications for drug delivery/bioavailability. Yet, this parameter has not been studied. In this work, gastric content was aspirated from patients before, immediately after, and the day after different bariatric procedures, and pH was immediately measured. Compared to pre-surgery (1.8), pH was increased one day after one-anastomosis gastric bypass (OAGB) and sleeve gastrectomy (LSG) by 3-4 pH units; pH immediately after these procedures was in between the other 2 time points. Post-OAGB pH was significantly higher than post-LSG (6.4 and 4.9, respectively). Prior adjustable gastric band did not significantly alter baseline pH. We then performed drug dissolution studies of the antiplatelet drugs dipyridamole and aspirin, mimicking pre-surgery, post-LSG and post-OAGB conditions, implementing our pH results and other relevant physiological parameters. Dipyridamole, a weak base, completely dissolved (100% of dose) under pre-surgery conditions, while dissolution was hampered under post-LSG (5%) and post-OAGB (0.25%) conditions, due to solubility limit. Aspirin was not released from enteric-coated tablet under pre-surgery or post-LSG gastric conditions, however, >75% dissolved within 15 min under post-OAGB gastric conditions, indicating potential failure of enteric coating, depending on the bariatric procedure. In conclusion, special care should be taken when using pH-dependent drugs and drug products after bariatric surgery, and the use of pH-independent formulations should be preferred. Overall, this research revealed the interim gastric pH after different bariatric procedures, and potentially important effects on post-bariatric oral drug delivery and treatment.

摘要

胃内 pH 值可能在减重手术后发生变化,从而影响药物的传递/生物利用度。然而,这一参数尚未得到研究。在这项工作中,从接受不同减重手术的患者术前、术后即刻和术后一天抽吸胃内容物,并立即测量 pH 值。与术前(1.8)相比,一次吻合胃旁路术(OAGB)和袖状胃切除术(LSG)后一天 pH 值增加了 3-4 个单位;术后即刻的 pH 值介于其他两个时间点之间。OAGB 术后 pH 值显著高于 LSG 术后(分别为 6.4 和 4.9)。先前的可调胃束带术并未显著改变基线 pH 值。然后,我们进行了抗血小板药物双嘧达莫和阿司匹林的药物溶出研究,模拟了术前、LSG 术后和 OAGB 术后的条件,实施了我们的 pH 值结果和其他相关生理参数。双嘧达莫是一种弱碱,在术前条件下完全溶解(100%剂量),而在 LSG 术后(5%)和 OAGB 术后(0.25%)条件下,由于溶解度限制,溶解受到阻碍。阿司匹林在术前或 LSG 术后胃条件下未从肠溶片释放,但在 OAGB 术后胃条件下 15 分钟内溶解超过 75%,表明根据减重手术,肠溶衣可能会失效。总之,在减重手术后使用 pH 依赖性药物和药物产品时应特别小心,应优先使用 pH 非依赖性制剂。总的来说,这项研究揭示了不同减重手术后的临时胃内 pH 值,以及对减重后口服药物传递和治疗的潜在重要影响。

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