In vitro assessment of ATP-binding cassette transporters and their functional genetic polymorphisms on fluoroquinolone accumulation in human embryonic kidney 293 recombinant cell lines
Abstract
Fluoroquinolone tissue distribution and cellular accumulation are hindered by efflux transporters, including ATP-binding cassette subfamily B member 1 (ABCB1), ATP-binding cassette subfamily G member 2 (ABCG2), and ATP-binding cassette subfamily C member 4 (ABCC4). Genetic polymorphisms (single-nucleotide polymorphisms) can impact transporter activity, leading to interindividual variability in the systemic and cellular pharmacokinetics of their substrates. This study assesses the impact of these transporters on moxifloxacin and ciprofloxacin (CIP) cellular accumulation in vitro, and the effect of common single-nucleotide polymorphisms in ABCB1 [c.1199G>A (rs2229109); common haplotype c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642)] and ABCG2 [c.421C>A (rs2231142)]. Recombinant human embryonic kidney (HEK) cell lines overexpressing wild-type or variant transporters were generated via stable plasmid transfection. The impact of transporter overexpression on fluoroquinolone cell disposition was assessed through accumulation experiments in the presence of specific inhibitors to establish the link between transporter expression and differential accumulation. Results indicated that ABCB1 overexpression reduced moxifloxacin cellular concentration by 30% but inconsistently with that of CIP and that zosuquidar or elacridar reversed these effects. ABCG2 had no impact. ABCC4 markedly reduced CIP accumulation by 25%, even at the basal level, an effect reversed…
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
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.