Arsenite-Induced Drug-Drug Interactions in Rats.

Autor:	Zhang J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Li W; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Liu Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., He Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Cheng Z; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Li X; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Chen Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Zhang A; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Peng Y; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.)., Zheng J; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), School of Pharmacy (J.Z., W.L., Y.L., Y.H., Z.C., X.L., Y.C., A.Z., J.Z.), Guizhou Medical University, Guiyang, Guizhou, P. R. China; State Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, P. R. China (A.Z.); and Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, P. R. China (Y.P., J.Z.) zhengneu@yahoo.com 2430885290@qq.com aihuagzykd@163.com yingpeng1999@163.com.
Jazyk:	angličtina
Zdroj:	Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2024 Jul 16; Vol. 52 (8), pp. 911-918. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1124/dmd.124.001772
Abstrakt:	Arsenite is an important heavy metal. Some Chinese traditional medicines contain significant amounts of arsenite. The aim of this study was to investigate subacute exposure of arsenite on activities of cytochrome P450 enzymes and pharmacokinetic behaviors of drugs in rats. Midazolam, tolbutamide, metoprolol, omeprazole, caffeine, and chlorzoxazone, the probe substrates for cytochrome P450 (CYP) s3A, 2C6, 2D, 2C11, 1A, and 2E, were selected as probe drugs for the pharmacokinetic study. Significant decreases in areas under the curves of probe substrates were observed in rats after consecutive 30-day exposure to As at 12 mg/kg. Microsomal incubation study showed that the subacute exposure to arsenite resulted in little change in effects on the activities of P450 enzymes examined. However, everted gut sac study demonstrated that such exposure induced significant decreases in intestinal absorption of these drugs by both passive diffusion and carrier-mediated transport. In addition, in vivo study showed that the arsenite exposure decreased the rate of peristaltic propulsion. The decreases in intestinal permeability of the probe drugs and peristaltic propulsion rate most likely resulted in the observed decreases in the internal exposure of the probe drugs. Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. SIGNIFICANCE STATEMENT: Exposure to arsenite may lead to the reduction of the efficiencies of pharmaceutical agents coadministered resulting from the observed drug-drug interactions. The present study, we found that P450 enzyme probe drug exposure was reduced in arsenic-exposed animals (areas under the curve) and the intestinal absorption of the drug was reduced in the animals. Subacute arsenic exposure tends to cause damage to intestinal function, which leads to reduced drug absorption. (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu