Pharmaceutical Sciences Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, P.O. Box 100494, Gainesville, FL 32610, USA.
Int J Antimicrob Agents. 2014 Oct;44(4):327-33. doi: 10.1016/j.ijantimicag.2014.06.011. Epub 2014 Jul 29.
Moxifloxacin is reported to have increased distribution into the prostate compared with older fluoroquinolones such as norfloxacin and ciprofloxacin, being able to reach tissue-to-plasma concentration ratios greater than unity. However, most of these studies use tissue homogenates derived from biopsy samples, which can lead to overestimation of free concentrations as fluoroquinolones tend to accumulate in the intracellular space. The aim of this study was to investigate moxifloxacin pharmacokinetics in rat prostate interstitial fluid by microdialysis. Tissue pharmacokinetics was assessed by implanting a small microdialysis catheter in the prostate gland. Blood samples were simultaneously collected for assessing plasma pharmacokinetics. Analysis of plasma (N=154) and microdialysis (N=344) concentrations after a single intravenous dose of 6 or 12mg/kg moxifloxacin was conducted in the non-linear mixed-effect modelling software NONMEM v.6 as well by a non-compartmental approach. Moxifloxacin showed a significant tissue distribution in the prostate (AUCprostate,ISF/fu·AUCplasma=1.24±0.37), 59% higher than the value obtained for levofloxacin in a previous study. A three-compartment model with non-linear kinetics could adequately describe moxifloxacin pharmacokinetics in terms of curve fitting and precision in parameter estimation. The developed pharmacokinetic model indicates that passive diffusion and active transport are the mechanisms involved in moxifloxacin distribution to the prostate. These findings suggest that moxifloxacin could be a better alternative to levofloxacin for the treatment of chronic bacterial prostatitis owing to its enhanced tissue penetration and higher AUCtissue/MIC ratios, even though it is not yet approved by the US FDA for this indication.
莫西沙星与诺氟沙星和环丙沙星等较老的氟喹诺酮类药物相比，据称其分布到前列腺组织中的量增加，能够达到组织-血浆浓度比大于 1。然而，这些研究中的大多数使用的是源自活检样本的组织匀浆，这可能导致游离浓度的高估，因为氟喹诺酮类药物往往会积聚在细胞内空间。本研究旨在通过微透析研究莫西沙星在大鼠前列腺间质液中的药代动力学。通过在前列腺中植入一个小的微透析导管来评估组织药代动力学。同时采集血样以评估血浆药代动力学。在 NONMEM v.6 非线性混合效应建模软件中以及通过非房室模型对单次静脉注射 6 或 12mg/kg 莫西沙星后血浆（N=154）和微透析（N=344）浓度进行分析。莫西沙星在前列腺中有明显的组织分布（AUCprostate,ISF/fu·AUCplasma=1.24±0.37），比以前的研究中左氧氟沙星的值高 59%。具有非线性动力学的三房室模型可以很好地描述莫西沙星的药代动力学，无论是在曲线拟合还是参数估计的精度方面。所开发的药代动力学模型表明，被动扩散和主动转运是莫西沙星分布到前列腺的机制。这些发现表明，莫西沙星可能是治疗慢性细菌性前列腺炎的更好选择，因为它具有增强的组织穿透性和更高的 AUCtissue/MIC 比值，尽管它尚未获得美国 FDA 批准用于该适应症。
