Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study

Abstract

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54–64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges

“…Similarly, it is unclear how oral mucositis impacts the rate of absorption. Oils can also be encapsulated for ingestion; however, this method of administration must be considered in the context of dysphagia and nausea/vomiting, which may impact the patient’s ability to swallow a capsule, or intestinal mucositis which may also influence the rate of absorption [ 127 ]. This underscores the need to conduct appropriate pharmacokinetic studies to understand how these unique factors associated with cancer, in particular active chemotherapy, impact the uptake and efficacy of cannabis.…”