Goodwin S D, Gallis H A, Chow A T, Wong F A, Flor S C, Bartlett J A
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Antimicrob Agents Chemother. 1994 Apr;38(4):799-804. doi: 10.1128/AAC.38.4.799.
Levofloxacin, the bacteriologically active isomer of ofloxacin, has microbiologic activity against many pathogens common in human immunodeficiency virus (HIV)-infected patients, including Mycoplasma species which may be cofactors in the progression of HIV disease. The purpose of this phase I, double-blind, randomized (1:1), placebo-controlled trial was to evaluate the pharmacokinetics and safety of levofloxacin hemihydrate in 10 asymptomatic HIV-infected males. Plasma concentrations by chiral high-performance liquid chromatography (HPLC) were evaluated for 48 h after a single 350-mg oral dose, at morning predose during the multiple-dosing phase, and for 72 h at steady state after a week of 350 mg every 8 h orally. Mean +/- standard deviation levofloxacin pharmacokinetic parameters (by noncompartmental moment method) after multiple dosing were as follows: area under the concentration-time curve, 31.24 +/- 5.60 mg.h/liter; apparent total body clearance, 11.18 +/- 1.76 liters/h; renal clearance, 8.63 +/- 2.82 liters/h; steady-state volume of distribution, 104.10 +/- 12.48 liters; and effective half-life, 6.50 +/- 0.51 h. Single-dose parameters were not significantly different from the multiple-dose parameters, with the exception of peak concentrations in plasma, which were 4.79 +/- 1.00 and 6.92 +/- 1.56 mg/liter for single- and multiple-dose data, respectively. Essentially identical parameter values were obtained from curve-fitting analysis when the entire 13-day plasma concentration profiles of the subjects were analyzed simultaneously by a two-compartmental distribution model. Levofloxacin pharmacokinetics in HIV-infected patients remained linear upon multiple dosing. The dosing regimen studied provides levels in plasma and urine well above those found to be effective in vitro against pathogens common in HIV-infected patients. Levofloxacin was well- tolerated in this group of asymptomatic HIV-infected males: there were no statistically significant differences in adverse effects in the two groups (P = 0.22). Use of placebo control helped to differentiate disease-related adverse effects from those related to the study drug.
左氧氟沙星是氧氟沙星的具有细菌学活性的异构体，对人类免疫缺陷病毒（HIV）感染患者中常见的许多病原体具有微生物活性，包括支原体属，支原体可能是HIV疾病进展的辅助因子。这项I期双盲随机（1:1）安慰剂对照试验的目的是评估10名无症状HIV感染男性中左氧氟沙星半水合物的药代动力学和安全性。在单次口服350mg剂量后48小时、多剂量阶段早晨给药前以及口服350mg每8小时一次，一周后达到稳态时评估72小时，通过手性高效液相色谱（HPLC）测定血浆浓度。多剂量给药后（采用非房室矩法）左氧氟沙星的平均药代动力学参数（±标准差）如下：浓度-时间曲线下面积，31.24±5.60mg·h/升；表观总体清除率，11.18±1.76升/小时；肾清除率，8.63±2.82升/小时；稳态分布容积，104.10±12.48升；有效半衰期，6.50±0.51小时。单剂量参数与多剂量参数无显著差异，但血浆峰浓度除外，单剂量和多剂量数据的血浆峰浓度分别为4.79±1.00和6.92±1.56mg/升。当通过二室分布模型同时分析受试者的整个13天血浆浓度曲线时，通过曲线拟合分析获得了基本相同的参数值。HIV感染患者多次给药后左氧氟沙星的药代动力学仍呈线性。所研究的给药方案在血浆和尿液中提供的水平远高于体外对HIV感染患者常见病原体有效的水平。左氧氟沙星在这组无症状HIV感染男性中耐受性良好：两组不良反应无统计学显著差异（P = 0.22）。使用安慰剂对照有助于区分与疾病相关的不良反应和与研究药物相关的不良反应。
