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蛛网膜下腔出血和择期神经外科手术后的肠道药物吸收:埃索美拉唑药代动力学的启示

Intestinal Drug Absorption After Subarachnoid Hemorrhage and Elective Neurosurgery: Insights From Esomeprazole Pharmacokinetics.

作者信息

Kranawetter Beate, Brockmöller Jürgen, Sindern Juliane, Hapke Anne, Bruns Ellen, Harnisch Lars-Olav, Moerer Onnen, Stenzig Justus, Mielke Dorothee, Rohde Veit, Abboud Tammam

机构信息

Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.

Institute of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany.

出版信息

Crit Care Med. 2025 Jan 1;53(1):e140-e150. doi: 10.1097/CCM.0000000000006512. Epub 2024 Nov 20.

Abstract

OBJECTIVES

Subarachnoid hemorrhage (SAH) may critically impair cardiovascular, metabolic, and gastrointestinal function. Previous research has demonstrated compromised drug absorption in this group of patients. This study aimed to examine the impact of SAH on gastrointestinal function and its subsequent effect on the absorption of enterally administered drugs, using esomeprazole as a probe drug.

DESIGN

Prospective observational cohort study.

SETTING

Academic hospital in Germany.

PATIENTS

We included 17 patients with high-grade SAH and 17 controls, comparable in age, sex, body weight, and renal function, who underwent elective cranial surgery.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Both groups received esomeprazole per standard protocol to prevent acid-associated mucosal damage, either orally or through a nasogastric tube. On day 4, esomeprazole was administered IV to estimate oral bioavailability. Esomeprazole serum concentrations were measured on days 1, 3, and 4 in both groups and on day 7 in the SAH group. Patients with high-grade SAH exhibited severely impaired drug absorption. Most patients showed no improvement in intestinal drug absorption even a week after hemorrhage.

CONCLUSIONS

Following SAH, significantly reduced drug absorption may be attributed to decreased intestinal motility and compromised intestinal mucosal function. Clinicians should anticipate the reduced effectiveness of enterally administered medications for at least seven days after high-grade SAH.

摘要

目的

蛛网膜下腔出血(SAH)可能严重损害心血管、代谢及胃肠功能。既往研究表明该组患者药物吸收受损。本研究旨在以埃索美拉唑作为受试药物,探讨SAH对胃肠功能的影响及其对肠内给药药物吸收的后续作用。

设计

前瞻性观察性队列研究。

地点

德国的一家学术医院。

患者

我们纳入了17例重度SAH患者和17名对照者,他们在年龄、性别、体重和肾功能方面具有可比性,均接受择期开颅手术。

干预措施

无。

测量指标及主要结果

两组均按照标准方案接受埃索美拉唑治疗,以预防酸相关黏膜损伤,给药途径为口服或经鼻胃管给药。在第4天,静脉注射埃索美拉唑以评估口服生物利用度。在第1、3和4天对两组患者测定埃索美拉唑血清浓度,在第7天对SAH组患者测定该浓度。重度SAH患者的药物吸收严重受损。多数患者在出血后一周内肠内药物吸收仍无改善。

结论

SAH后药物吸收显著降低可能归因于肠道蠕动减弱和肠黏膜功能受损。临床医生应预计在重度SAH后至少七天内肠内给药的疗效会降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/102e/11698135/82ed4cbc2f44/ccm-53-e140-g001.jpg

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