Naora K, Katagiri Y, Ichikawa N, Hayashibara M, Iwamoto K
Department of Pharmacy, Shimane Medical University Hospital, Izumo, Japan.
J Pharmacol Exp Ther. 1991 Sep;258(3):1033-7.
The effects of fenbufen on the transport of ciprofloxacin (CPFX) into the brain and cerebrospinal fluid (CSF) were investigated in rats. Periodically after a bolus i.v. dose of CPFX (10 mg/kg), alone or with fenbufen (20 mg/kg), to rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the animal after sacrifice by microwave irradiation. Serum levels of CPFX in the terminal phase were significantly elevated by the coadministration with fenbufen. However, the extent of CPFX binding to serum protein was not affected by fenbufen. Immediately after the coadministration with fenbufen, brain and CSF levels of CPFX were raised by about 15 to 70% and 70 to 100%, respectively. Both brain/serum unbound and CSF/serum unbound level ratios were increased by fenbufen at relatively early periods after drug injection. Analysis based on physiological models indicated that fenbufen significantly increased the apparent diffusion clearances of CPFX across blood-brain and blood-CSF barriers. These findings suggest that coadministered fenbufen may facilitate the entry of CPFX into the central nervous system not only by elevation of serum level but also by enhancement of permeability across the blood-brain or blood-CSF barrier.
在大鼠中研究了芬布芬对环丙沙星（CPFX）进入脑和脑脊液（CSF）转运的影响。给大鼠静脉注射大剂量CPFX（10mg/kg），单独或与芬布芬（20mg/kg）联合给药后，定期收集CSF和血液样本，然后在通过微波辐射处死后从动物体内迅速取出全脑。与芬布芬联合给药后，终末期CPFX的血清水平显著升高。然而，芬布芬不影响CPFX与血清蛋白的结合程度。与芬布芬联合给药后，CPFX的脑和CSF水平立即分别升高约15%至70%和70%至100%。在给药后相对较早的时期，芬布芬使脑/血清未结合水平和CSF/血清未结合水平比率均升高。基于生理模型的分析表明，芬布芬显著增加了CPFX跨血脑屏障和血脑脊液屏障的表观扩散清除率。这些发现表明，联合使用芬布芬可能不仅通过提高血清水平，而且通过增强跨血脑屏障或血脑脊液屏障的通透性，促进CPFX进入中枢神经系统。
