Summary
Transport of 11 quinolones at the blood-brain barrier (BBB) was studied in vitro by using primarily cultured rat brain capillary endothelial cells (BCECs) and in vivo brain-to-plasma concentration ratios. In vitro, when cells reached confluence, a time course of quinolone uptake was recorded by incubation with a medium contraining quinolones 20 μg/ml at 37°C. A simple two-compartment model was used for fitting the uptake time course and corresponding uptake parameters were estimated. In vivo rats were anesthetized, after in 10 mg/kg of quinoloes followed by infusion of 4 mg/kg/h for 2 hours, the drug concentrations in plasma and brain were measure and brain-to-plasma concentration ratios were calculated. Result showed that Sparfloxacin and prulifloxacin have higher uptakes by BCECs and brain-to-plasma concentration ratios, compared with other quinolones, which indicated that the two drugs more easily penetrate into BBB. A good correlation between uptakes by BCECs and brain-to-plasma concentration ratios was found. These results demonstrated uptakes by BCECs in vitro might give prediction of brain-to-plasma ratio for quinolones.
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References
Moellering Jr R.C. (1996): The place of quinolones in everyday clinical practice. Chemothera. 42:54–61.
Ooie T., Suzuki H., Terasaki T., Sugiyama Y. (1997): Quantitative brain microdialysis study on the mechanism of quinoloes distribution in the central system. Drug Metab. Dispos. 25:784–89.
Akahane K., Sekiguchi M., Une T., Osada Y. (1989): Structure-epileptogenicity relationship of quinolones with special reference to their interaction with g-aminobutyric acid receptor sites. Antimicrob. Agents Chemother. 33:1704–8.
Murata M, Tamai I., Kato H., Nagata O., Kato H., Tsuji A. (1999): Efflux Transport of a New Quinolone Antibacterial Agent, HSR-903, across the Blood-Brain Barrier. J. Pharmacol. Ex. Ther. 290:51–7.
Tamai I., Yamashita J., Kido Y., Ohnari A., Sai Y., Shima Y., Naruhashi K., Koizumi S., Tsuji A. (2000): Limited Distribution of New Quinolone Antibacterial Agents into Brain Caused by Multiple Efflux Transporters at the Blood-Brain Barrier. J. Pharmacol. Exp. Ther. 295:146–52.
6. de Lange E.C., Marchand S., van den Berg D., van der Sandt I.C., de Boer A.G., Delon A., Bouquet S., Couet W. (2000): In vitro and in vivo investigations on fluoroquinolones; effects of the P-glycoprotein efflux transporter on brain distribution of Sparfloxacin. Eur. J. Pharm. Sci. 12: 85–93.
Hanse D.K., Scott D.O., Otis K.W., Lunte S.M. (2002): Comaprison fo in vitro BBMEC permebility and in CNS uptake by microdialysis sampling. J. Pharm. Biomed. Anal. 27:945–58.
Saheki A., Terasaki T., Tamai I., Tsuji A. (1994): In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm. Res. 11:305–11.
Zhang L, Liu X.D., Xie L., Wang G.J. (2003): P-glycoprotein restricted transport of nimodipine across blood-brain barrier. Acta Pharmacol. sIN. 24:903–6.
Bradford M.M. (1976): A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–54.
Ooie T., Suzuki H., Terasaki T., Sugiyama Y. (1996): Comparative distribution of quinolone antibiotics in cerebrospinal fluid and brain in rats and dogs. J. Pharmacol. Exp. Ther. 278:590–6.
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Project supporting by national «863» item plan (No 2003AA2Z347A)
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Liu, X.D., Wang, D.W. & Xie, L. Correlation between quinolone uptakes by BCECs in vitro and brain-to-plasma concentration ratios in rats. European Journal of Drug Metabolism and Pharmacokinetics 30, 249–254 (2005). https://doi.org/10.1007/BF03190628
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DOI: https://doi.org/10.1007/BF03190628