Lactobacillus rhamnosus induces CYP3A and changes the pharmacokinetics of verapamil in rats
| Autor: | Shengbo Huang, Yuanjin Zhang, Jie Liu, Zongjun Liu, Yi Cheng, Xin Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.drug_class Metabolite Calcium channel blocker Pharmacology Gut flora Toxicology digestive system Gene Expression Regulation Enzymologic law.invention Rats Sprague-Dawley chemistry.chemical_compound Probiotic fluids and secretions Pharmacokinetics Lactobacillus rhamnosus law medicine Animals Cytochrome P-450 CYP3A biology Lacticaseibacillus rhamnosus Chemistry Probiotics food and beverages Norverapamil General Medicine Calcium Channel Blockers biology.organism_classification Gastrointestinal Microbiome Rats Verapamil Area Under Curve Gene Deletion Half-Life medicine.drug |
| Zdroj: | Toxicology Letters. 352:46-53 |
| ISSN: | 0378-4274 |
| Popis: | Verapamil, a calcium channel blocker, has been approved as the first-line drug for treatment of angina pectoris, hypertension and supraventricular tachycardia. Lactobacillus rhamnosus, one of the normal strains in human intestinal tract, is very popular in the probiotic market for conferring a health benefit on the host. This report investigated the potential of gut microbiota-drug interactions between lactobacillus rhamnosus and verapamil via using wild type (WT) and Cyp3a1/2 knockout (KO) rats. In WT rats, administration of Lactobacillus rhamnosus for 14 days decreased systemic exposure of verapamil and increased its metabolite norverapamil in vivo, and resulted in gut microbiota-drug interactions. In Cyp3a1/2 KO rats, however, this interaction disappeared. Further studies found that Lactobacillus rhamnosus induced CYP3A activity and expression, and changed the composition of gut microbiota, thus changing the pharmacokinetics of verapamil. These results demonstrated the interaction between lactobacillus rhamnosus and verapamil, and indicated that the effect of gut microbiota on metabolic enzymes cannot be ignored. |
| Databáze: | OpenAIRE |
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