Abstract
Antimicrobial prophylaxis is increasingly being used in patients with hematological malignancies receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). However, few studies have focused on the potential impact of gastrointestinal mucositis (GI-M), a frequently observed side effect of chemotherapy in patients with cancer that affects the gastrointestinal microenvironment, on drug absorption. In this review, we discuss how chemotherapy leads to an overall loss of mucosal surface area and consequently to uncontrolled transport across the barrier. The barrier function is depending on intestinal luminal pH, intestinal motility, and diet. Another factor contributing to drug absorption is the gut microbiota, as it modulates the bioavailability of orally administrated drugs by altering the gastrointestinal properties. To better understand the complex interplay of factors in GI-M and drug absorption we suggest: (i) the longitudinal characterization of the impact of GI-M severity on drug exposure in patients, (ii) the development of tools to predict drug absorption, and (iii) strategies that allow the support of the gut microbiota. These studies will provide relevant data to better design strategies to reduce the severity and impact of GI-M in patients with cancer.
Highlights
The gastrointestinal microincreased inflammation and resulting consequentlyin barrier disruption. This results in the disruption of the gut microbiota, environment can be disturbed by external insults as chemotherapy, leading increased inalterations in gastric/intestinal pH, alterations of intestinal motility,such and bacterial translocation
Kuchay et al 2015 showed that a single dose of 5-fluoruracil chemotherapy in rats is enough to cause a significant reduction in the activity of brush-border enzymes such as alkaline phosphatase, sucrase, and lactase, a result that needs to be reproduced in humans [56]
A growing body of research has suggested the fundamental role of the gut microbiota in the maintenance of intestinal homeostasis and gut resilience during chemotherapy [77,78]
Summary
The complexity of the situation becomes clear: people with cancer are administered life-saving antimicrobials with no understanding of how GI-M impacts their bioavailability and efficacy Despite this clinical paradox, few studies have been performed to understand whether such profound changes in the GI environment affect the absorption and efficacy of anti-infective therapies in the context of cancer treatment. The gastrointestinal microincreased inflammation and resulting consequentlyin barrier disruption This results in the disruption of the gut microbiota, environment can be disturbed by external insults as chemotherapy, leading increased inalterations in gastric/intestinal pH, alterations of intestinal motility,such and bacterial translocation. This results in the disruption of the gut microbiota, alterations in gastric/intestinal pH, alterations of intestinal motility, and bacterial translocation Together, these altered physiological/morphological functions potentially impair drug absorption.
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