Multiple drug transporters contribute to the brain transfer of levofloxacin
Abstract
Abstract Aims The aim of this study was to assess the influence of the major transporters at blood–brain barrier and blood–cerebrospinal fluid barrier on levofloxacin (LVFX) pharmacokinetics in rat. To explore the different effects of transporters on drug concentrations in cerebrospinal fluid (CSF) and brain extracellular fluid (ECF). Methods High‐performance liquid chromatography coupled with microdialysis was used to continuously and synchronously measure unbound concentrations of LVFX in rat blood, hippocampal ECF, and lateral ventricle CSF for comprehensive characterization of brain pharmacokinetics. The role of transporters in the brain efflux mechanism of LVFX was analyzed in the absence and presence of various transporter inhibitors. Results Following LVFX (50 mg/kg) administration, the unbound partition coefficient of LVFX in brain ECF and CSF (Kp,uu,ECF and Kp,uu,CSF) were 34.0 ± 1.7% and 41.2 ± 2.4%, respectively. When probenecid was coadministered with LVFX, the AUC and the mean residence time (MRT) in rat blood increased significantly (p < 0.05). After MK571 intervention, 1.35‐fold and 1.16‐fold increases in Kp,uu,ECF and Kp,uu,CSF were observed, respectively (p < 0.05). Treatment with Ko143 increased the levels of LVFX in brain ECF. The difference in LVFX concentration in brain ECF and CSF was <3‐fold with or without treatment with transporter inhibitors. Conclusion Efflux of LVFX from the central nervous system (CNS) involves multidrug resistance‐associated…
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.