Sullivan J T, Lettieri J T, Liu P, Heller A H
Bayer Corporation, Pharmaceutical Division, West Haven, Connecticut 06516-4175, USA.
Clin Pharmacokinet. 2001;40 Suppl 1:11-8. doi: 10.2165/00003088-200140001-00002.
Moxifloxacin is a new 8-methoxyfluoroquinolone with a broad antibacterial spectrum. The purpose of the present study was to determine the effects of age and gender on pharmacokinetics, surrogate pharmacodynamics, safety and tolerability of a single dose of moxifloxacin.
This was a randomised, double-blind, placebo-controlled, parallel-group single dose trial in young and elderly healthy volunteers.
The study included 36 volunteers in 3 age and gender groups: young males (mean age 32 years), elderly males (mean age 74 years), and elderly females (mean age 74 years).
Participants received either a single 200mg oral dose of moxifloxacin (8/group) or placebo (4/group). Blood samples for moxifloxacin pharmacokinetics were obtained before and up to 48 hours after administration. Urine samples were collected for pharmacokinetics, and volunteers were monitored for clinical adverse events and laboratory abnormalities.
Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were higher in elderly females than in elderly males; however, when normalised for bodyweight, these pharmacokinetic parameters were not significantly different between the groups. Moreover, the plasma pharmacokinetics in elderly males were not meaningfully different from those in young males. Elimination half-life averaged 12 to 13 hours for the 3 groups. Surrogate pharmacodynamic measures were derived using AUC/MIC (minimal inhibitory concentration) and Cmax/MIC ratios. These assessments indicated that, given the linear pharmacokinetics of moxifloxacin previously demonstrated, a dose of 400mg would produce mean Cmax/MIC values in the different subgroups ranging from 10.4 to 15.4 for an MIC of 0.25, and 20.8 to 30.8 for an MIC of 0.125. The corresponding ranges of projected AUC/MIC ratios would be 112 to 158 for an MIC of 0.25, and 224 to 314 for an MIC of 0.125. The accepted target values of AUC/MIC and Cmax/MIC for quinolones are 125 and 10, respectively. There were no serious adverse events or differences in adverse event profiles between the groups.
Moxifloxacin does not exhibit age- or gender-dependent pharmacokinetics. Oral doses of 200 to 400mg yield effective antibacterial concentrations on the first day of administration.
莫西沙星是一种新型8-甲氧基氟喹诺酮类药物，抗菌谱广。本研究旨在确定年龄和性别对单剂量莫西沙星的药代动力学、替代药效学、安全性和耐受性的影响。
这是一项针对年轻和老年健康志愿者的随机、双盲、安慰剂对照、平行组单剂量试验。
该研究纳入了36名志愿者，分为3个年龄和性别组：年轻男性（平均年龄32岁）、老年男性（平均年龄74岁）和老年女性（平均年龄74岁）。
参与者接受单剂量200mg口服莫西沙星（每组8人）或安慰剂（每组4人）。在给药前及给药后长达48小时采集血样用于莫西沙星药代动力学分析。收集尿样用于药代动力学分析，并监测志愿者的临床不良事件和实验室异常情况。
老年女性的血浆最大浓度（Cmax）和血浆浓度-时间曲线下面积（AUC）高于老年男性；然而，按体重标准化后，这些药代动力学参数在各组之间无显著差异。此外，老年男性的血浆药代动力学与年轻男性无明显差异。3组的消除半衰期平均为12至13小时。使用AUC/MIC（最低抑菌浓度）和Cmax/MIC比值得出替代药效学指标。这些评估表明，鉴于先前证明的莫西沙星线性药代动力学，对于最低抑菌浓度为0.25的情况，400mg剂量在不同亚组中产生的平均Cmax/MIC值范围为10.4至15.4，对于最低抑菌浓度为0.125的情况，该值范围为20.8至30.8。对于最低抑菌浓度为0.25的情况，预计的AUC/MIC比值相应范围为112至158，对于最低抑菌浓度为0.125的情况，该值范围为224至314。喹诺酮类药物公认的AUC/MIC和Cmax/MIC目标值分别为125和10。各组之间无严重不良事件，不良事件谱也无差异。
莫西沙星不存在年龄或性别依赖性药代动力学。口服200至400mg剂量在给药第一天即可产生有效的抗菌浓度。
