Journal
CHEMISTRYSELECT
Volume 6, Issue 29, Pages 7476-7481Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/slct.202102122
Keywords
Biological activity; Drug-drug interactions; Levofloxacin; Molecular Docking; P-glycoprotein
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Funding
- Scientific and Technological Research Council of Turkey 1002 Rapid Support Program [TUBITAK-110O942]
- Research Fund of Selcuk University [SU-BAP-11102014]
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This study investigated the effects of FEX and DEX with P-gp modulators on the distribution of LVX in rat brain, testicle, and plasma. The results showed that the dose and time of DEX administration could affect the passage of LVX to the brain and testicle tissue.
P-glycoprotein (P-gp), a transporter membrane protein, plays an important role in various physiological and physiopathological conditions, drug-drug and drug-food interactions, and multi-drug resistance. Nowadays, P-gp modulators are used consciously to treat some specific diseases, such as cancer and poisoning. Levofloxacin (LVX), a P-gp substrate, may cause the stimulation of the central nervous system. The aim of this study was to determine the effects of fexofenadine (FEX) and dexamethasone (DEX) with P-gp modulators on the distribution of LVX in rat brain, testicle, and plasma. In the in vivo section of the study, LVX concentrations in tissue and plasma samples were detected by high-performance liquid chromatography. In addition, in silico molecular docking studies were conducted to elucidate interactions between P-gp and drugs. The administration of DEX at a low dose and minute 30 reduced the LVX passage to the brain, while the administration of DEX at a high dose and hour 2 increased the LVX passage to the brain, testicle tissue, and plasma. MM-GBSA.G values of FEX, DEX, and LVX were calculated to be 80.95, 57.74, and 52.12 kcal/mol, respectively. The results of this study reported that DEX, known as a P-gp inductor, may show inhibitory activity based on dose, tissue, and time of application.
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