Pharmacokinetics and tolerance of ciprofloxacin after sequential increasing oral doses
Pharmacokinetics and tolerance of ciprofloxacin after sequential increasing oral doses
复制标题
连续增加口服剂量后环丙沙星的药代动力学和耐受性
DOI：
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发表时间：
1986
影响因子：
4.9
通讯作者：
T. Kerkering
中科院分区：
文献类型：
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作者：
T. Tartaglione;A. Raffalovich;W. Poynor;A. Espinel;T. Kerkering
12名健康男性志愿者连续口服环丙沙星250、500、750和1,000 mg，观察其药代动力学和安全性。假设表观零级吸收速率，通过双指数分布和消除最佳描述个体和平均数据。根据个体数据测定的血清峰浓度发生在每次给药后约1.5 h，范围为0.42 - 4.2 μ g/ml;平均峰浓度与剂量成比例增加。根据平均数据确定的曲线下面积也与剂量成比例。对于250、500、750和1，000 mg剂量，根据汇总数据计算的平均消除半衰期分别为4.1、4.1、6.9和6.3 h。750和1，000 mg剂量后的半衰期较长，但曲线下面积值成比例，表明这些剂量后吸收的环丙沙星比例较小，但不能排除非线性动力学。每次给药后12和24 h的平均血清浓度分别大于或等于0.08和0.01 μ g/ml。给药后至少12 h的尿浓度范围为30 - 500 μ g/ml，每次给药后24 h大于或等于9 μ g/ml。在24小时内，尿中原型环丙沙星的回收率范围为28%至44%。每种剂量的平均肾脏清除率范围为300至500 ml/min。环丙沙星耐受性良好，未观察到显著的临床或实验室异常。
The pharmacokinetics and safety of orally administered ciprofloxacin (Bay o 9867) were examined in 12 healthy male volunteers who received sequential doses of 250, 500, 750, and 1,000 mg. The individual and mean data were best described by biexponential disposition and elimination, assuming an apparent zero-order rate of absorption. The peak serum concentrations determined from the individual data occurred at approximately 1.5 h after each dose and ranged from 0.42 to 4.2 micrograms/ml; the mean peak concentrations increased in proportion to the dose. The areas under the curve determined from the mean data were also proportional with respect to dose. The mean elimination half-lives calculated from pooled data were 4.1, 4.1, 6.9, and 6.3 h for doses of 250, 500, 750, and 1,000 mg, respectively. Longer half-lives but proportional area-under-the-curve values after the 750- and 1,000-mg doses implied that smaller fractions of ciprofloxacin were absorbed after these doses, although nonlinear kinetics could not be ruled out. The mean serum concentrations 12 and 24 h following each dose were greater than or equal to 0.08 and 0.01 micrograms/ml, respectively. The urinary concentrations ranged from 30 to 500 micrograms/ml for at least 12 h after administration and were greater than or equal to 9 micrograms/ml at 24 h following each dose. The urinary recovery level of unchanged ciprofloxacin over a 24-h period ranged from 28 to 44%. The mean renal clearances for each dose ranged from 300 to 500 ml/min. Ciprofloxacin was well tolerated, and no significant clinical or laboratory abnormalities were observed.