The epidemic of loperamide abuse and misuse in the patients for the alternative to opioids has become an increasing worldwide concern and has led to considerations about the potential for drug-drug interactions between loperamide and other combined drugs, especially inhibitors of cytochrome P450 (CYP450) enzymes, such as axitinib. This study assessed the effects of axitinib on the metabolism of loperamide and its main metabolite N-demethylated loperamide in rats and in rat liver microsomes (RLM), human liver microsomes (HLM) and recombinant human CYP3A4*1. The concentrations of both compounds were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The exposures (AUC, AUC and C) of loperamide and N-demethylated loperamide showed a conspicuous increase when loperamide was co-administered with axitinib. The T of loperamide increased while CLz/F decreased under the influence of axitinib. In vitro, axitinib inhibited loperamide metabolism with the IC of 18.34 μM for RLM, 1.705 μM for HLM and 1.604 μM for CYP3A4*1, and it was confirmed as a non-competitive inhibitor in all enzymes. Taken together, the results indicated that axitinib had an obvious inhibitory impact on loperamide metabolism both in vivo and in vitro. Thus, more attention should be paid to the concurrent use of loperamide and axitinib to reduce the risk of unexpected clinical outcomes.
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http://dx.doi.org/10.1016/j.cbi.2019.108744 | DOI Listing |
Basic Clin Pharmacol Toxicol
February 2025
Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
New psychoactive substances (NPS) are health-hazardous through unpredictable toxicity and effects and largely unknown epidemiology, motivating studies of the latter. Up to 138 NPS were retrospectively identified using liquid chromatography-high resolution mass spectrometry data from all 34 183 oral fluid drug samples collected in one Swedish health care region 2019-2020 representing 9468 psychiatric and addiction care patients. In total, 618 findings representing 58 NPS were detected in 481 samples from 201 patients.
View Article and Find Full Text PDFTherap Adv Gastroenterol
January 2025
Operative Unit of Clinical Pharmacology and Pharmacovigilance, Renato Dulbecco University Hospital, Catanzaro, Italy.
Acute infectious diarrhea (AID) represents an important clinical entity both regarding morbidity and mortality rates, even in industrialized countries, and it leads to one of the major public health burdens, among gastroenterological diseases, with significant healthcare costs. Oral rehydration solution is the cornerstone of the therapy, but despite its proven efficacy in avoiding dehydration, it is still underused as it does not reduce the duration of diarrhea; hence, it is perceived as ineffective by caregivers. In this narrative review, we collected literature regarding the use of racecadotril, deeply discussing its role in the treatment of AID in both adults and children.
View Article and Find Full Text PDFFood Funct
January 2025
Institute of Human Behavior & Genetics, Korea University, Seoul 02841, Republic of Korea.
This study investigated the effects of on alleviating loperamide-induced constipation. To evaluate the efficacy of in Sprague-Dawley (SD) rats, fecal parameters, the intestinal transit rate, and changes in intestinal mucosal cells were measured through histological analysis. Additionally, serotonin levels, water absorption, tight junction-related gene expression, and the cecal short-chain fatty acid (SCFA) content were analyzed.
View Article and Find Full Text PDFAutophagy
January 2025
Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.
View Article and Find Full Text PDFCureus
December 2024
Rheumatology, Rochester Regional Health, Rochester, USA.
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