Xiao Y, Lu Y, Kang Z, Hou F, Wang S, Li T, Liu Y, Xia Y
Institute of Clinical Pharmacology, First Hospital, Peking University, #38 Xueyuan Road, Haidian District, Beijing, China.
Int J Clin Pharmacol Ther. 2008 Apr;46(4):172-9. doi: 10.5414/cpp46172.
To evaluate the tolerability and pharmacokinetics characteristics of antofloxacin hydrochloride, a fluoroquinolone developed in China, after multiple oral doses in healthy male Chinese volunteers.
13 subjects took 300 mg of antofloxacin hydrochloride once daily for 7 days. Safety was evaluated on Days 0, 2, 4 and 8. Blood and urine samples for pharmacokinetics analysis were taken at designated time points. HPLC was used to assay the serum and urine concentration of antofloxacin.
A total of 12 subjects completed the trial and 1 volunteer was dropped because of a skin rash 2 h after the drug was administered. 1 volunteer had a prolonged prothrombin time (PT), another had a serum alanine aminotransferase (ALT) elevation and a third had increases in aspartate aminotransferase (AST) and I(3)-glutamyltransferase (I(3)-GT). No other complaints were reported during the trial. The steady state serum concentration on a daily 300 mg oral dose was obtained at 96 h. The pharmacokinetics parameters at steady state were: t(max)1.19 A+/- 0.59 h, C(max) 4.49 A+/- 0.81 mg/l, C(min) 1.35 A+/- 0.33 mg/l, AUC(ss) 74.74 A+/- 12.58 mg/l A h, C(av) 3.11 A+/- 0.52 mg/l, t(1/2beta) 20.75 A+/- 2.93 h, PTF 102.13 A+/- 23.92%. The urinary elimination of antofloxacin over 120 h after the last dose was approximately 62%. C(max) in steady state was 50% higher compared to data for Day 1 after a single dose administration.
The results indicated that 300 mg antofloxacin hydrochloride once daily oral administration is safe, but can lead to high drug concentrations. This should be evaluated further.
评估中国研发的氟喹诺酮类药物盐酸安妥沙星在健康中国男性志愿者多次口服给药后的耐受性和药代动力学特征。
13名受试者每日一次口服300mg盐酸安妥沙星，共服用7天。在第0、2、4和8天评估安全性。在指定时间点采集血样和尿样用于药代动力学分析。采用高效液相色谱法测定血清和尿液中安妥沙星的浓度。
共有12名受试者完成试验，1名志愿者因给药后2小时出现皮疹而退出。1名志愿者凝血酶原时间（PT）延长，另1名志愿者血清丙氨酸氨基转移酶（ALT）升高，第3名志愿者天门冬氨酸氨基转移酶（AST）和γ-谷氨酰转移酶（γ-GT）升高。试验期间未报告其他不良反应。每日口服300mg剂量时，在96小时达到稳态血清浓度。稳态药代动力学参数为：t(max)1.19±0.59小时，C(max)4.49±0.81mg/L，C(min)1.35±0.33mg/L，AUC(ss)74.74±12.58mg/L·h，C(av)3.11±0.52mg/L，t(1/2β)20.75±2.93小时，PTF102.13±23.92%。末次给药后120小时内安妥沙星的尿排泄率约为62%。稳态时的C(max)比单次给药后第1天的数据高50%。
结果表明，每日一次口服300mg盐酸安妥沙星是安全的，但可导致较高的药物浓度。对此应进一步评估。
