Pea Federico, Pavan Federica, Lugatti Emilio, Dolcet Flavio, Talmassons Giovanni, Screm Maria Consuelo, Furlanut Mario
Department of Experimental and Clinical Pathology and Medicine, Institute of Clinical Pharmacology and Toxicology, Medical School, University of Udine, Udine, Italy.
Clin Pharmacokinet. 2006;45(3):287-95. doi: 10.2165/00003088-200645030-00004.
To assess the pharmacokinetic and pharmacodynamic behaviour of moxifloxacin in 15 consecutive elderly patients with acute exacerbation of chronic bronchitis (AECB) treated with the fixed oral moxifloxacin 400 mg/day regimen with the intent of verifying which degree of exposure may be ensured by this standard regimen against AECB pathogens.
This was an open-label, observational, pharmacokinetic-pharmacodynamic study. Blood samples were collected at steady state at appropriate intervals. Moxifloxacin plasma concentrations were analysed by means of high-performance liquid chromatography. Standard pharmacokinetic parameters and pharmacodynamic determinants (peak concentration [C(max)]/minimum inhibitory concentration [MIC], area under the plasma concentration-time curve during the 24-hour observational period [AUC(24)]/MIC, pharmacodynamic breakpoints [PDBPs]) were assessed.
The mean estimated pharmacokinetic parameters (C(max) 4.40 mg/L at 1.4 hours, AUC(24) 42.67 mg . h/L, elimination half-life 12.55 hours, total body clearance 0.16 L/h/kg) were generally similar to those observed in both young and elderly historic controls (except for higher-dose normalised C(max) and lower volume of distribution of the central compartment). Median C(max)/MIC and AUC(24)/MIC ratios for moxifloxacin in the fully assessable cases were, respectively, 67.5 and 823.9 against Streptococcus pneumoniae, 25 and 310.2 against Moraxella catharralis and 416.5 and 3647.5 against Haemophilus influenzae. Mean estimates of PDBP for achieving C(max)/MIC values of 12.2 and AUC(24)/MIC values of 125 were 0.36 and 0.35 mg/L, respectively.
In patients with AECB the pharmacokinetic behaviour of moxifloxacin is not significantly altered by aging processes. This is consistent with moxifloxacin being metabolised mainly by means of phase II hepatic reactions, the activity of which was shown not to decline with age. Both the pharmacokinetic and pharmacodynamic analyses suggest that moxifloxacin 400 mg/day may be a valid therapeutic approach in the treatment of AECB in the elderly. Of note, the unmodified pharmacokinetic behaviour with no need for age-related dosage adjustments combined with the once-daily administration favouring compliance and the low potential for drug-drug pharmacokinetic interactions in case of polytherapy, make moxifloxacin particularly attractive in the treatment of elderly subpopulations at a very high risk of AECB.
评估15例连续的老年慢性支气管炎急性加重期（AECB）患者口服莫西沙星400mg/日固定剂量方案后的药代动力学和药效学行为，旨在验证该标准方案针对AECB病原体可确保何种程度的暴露。
这是一项开放标签、观察性的药代动力学-药效学研究。在稳态时于适当间隔采集血样。采用高效液相色谱法分析莫西沙星血浆浓度。评估标准药代动力学参数和药效学决定因素（峰浓度[C(max)]/最低抑菌浓度[MIC]、24小时观察期内血浆浓度-时间曲线下面积[AUC(24)]/MIC、药效学断点[PDBP]）。
平均估算的药代动力学参数（1.4小时时C(max)为4.40mg/L，AUC(24)为42.67mg·h/L，消除半衰期为12.55小时，总体清除率为0.16L/h/kg）通常与年轻和老年历史对照者中观察到的参数相似（除了较高剂量标准化C(max)和中央室分布容积较低）。在完全可评估病例中，莫西沙星针对肺炎链球菌的C(max)/MIC和AUC(24)/MIC比值中位数分别为67.5和823.9，针对卡他莫拉菌分别为25和310.2，针对流感嗜血杆菌分别为416.5和3647.5。达到C(max)/MIC值为12.2和AUC(24)/MIC值为125时PDBP的平均估算值分别为0.36和0.35mg/L。
在AECB患者中，衰老过程未显著改变莫西沙星的药代动力学行为。这与莫西沙星主要通过II期肝脏反应代谢一致，而该反应的活性并未随年龄下降。药代动力学和药效学分析均表明，莫西沙星400mg/日可能是治疗老年AECB的有效治疗方法。值得注意的是，药代动力学行为未改变，无需根据年龄调整剂量，加上每日一次给药有利于依从性，且在联合治疗时药物-药物药代动力学相互作用可能性低，使得莫西沙星在治疗AECB极高风险的老年亚群中特别有吸引力。
