Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans
Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans
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AM-1155（一种新型 6-氟-8-甲氧基喹诺酮）在人体中的单剂量和多剂量药代动力学
DOI：
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发表时间：
1995
影响因子：
4.9
通讯作者：
H. Uchida
中科院分区：
文献类型：
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作者：
M. Nakashima;T. Uematsu;K. Kosuge;H. Kusajima;T. Ooie;Y. Masuda;R. Ishida;H. Uchida
在健康男性志愿者中，研究了AM-1155（一种新的6-氟-8-甲氧基喹诺酮）的药代动力学，受试者口服100、200、400或600 mg单次给药和300 mg多次给药，每日两次，共6.5天（共13次）。在整个研究期间，AM-1155在每例受试者中均耐受良好。在单次给药研究中，血清浓度在1 - 2 h之间达到峰值，100、200、400和600 mg剂量下的峰浓度分别为0.873、1.71、3.35和5.41 μ g/ml。消除半衰期为7至8小时，与剂量无关。原型药物主要经尿液排泄，82 - 88%的剂量持续72小时。单次经口给予400 mg剂量后，原型药物的粪便回收率为5.7%，持续72 h。代谢物的尿液排泄量极低。血清蛋白结合率为20%，与血清浓度无关。唾液中的浓度约为血清中浓度的80%。除了浓度-时间曲线下面积略有下降外，进食对AM-1155的药代动力学参数和尿排泄无影响。丙磺舒合并给药延长了消除半衰期，增加了浓度-时间曲线下面积，降低了原型药物的表观总清除率、肾清除率、尿回收率和排泄率（AM-1155的固有肾清除率/肌酐清除率）。这表明肾小管分泌有助于AM-1155的肾脏排泄。在多次给药研究中，血清和尿液中AM-1155的浓度在2 - 3天内达到稳态。血清中的测定浓度与模拟曲线拟合良好，反映了AM-1155线性药代动力学的持续性。总之，AM-1155由于其有效的抗菌活性和有利的药代动力学，预计将在临床上有用。
The pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, was examined in healthy male volunteers after the oral administration of a single dose of 100, 200, 400, or 600 mg and multiple doses of 300 mg twice daily for 6.5 days (13 total doses). Throughout the whole study period, AM-1155 was well tolerated in every subject. In the single-dose study, the concentrations in serum reached a peak between 1 and 2 h, and the peak concentrations were 0.873, 1.71, 3.35, and 5.41 micrograms/ml at the doses of 100, 200, 400, and 600 mg, respectively. The elimination half-life was 7 to 8 h, independently of the doses. The unchanged drug was excreted mainly in the urine, with 82 to 88% of the doses appearing for 72 h. The fecal recovery of the unchanged drug amounted to 5.7% for 72 h after a single oral administration of a 400-mg dose. Urinary excretion of metabolites was minimal. The serum protein binding was 20%, independently of the concentrations in serum. The concentrations in saliva were approximately 80% of those in serum. The intake of food had no effect on the pharmacokinetic parameters and urinary excretion of AM-1155 except the slight decrease in area under the concentration-time curve. The concurrent administration of probenecid prolonged the elimination half-life, increased the area under the concentration-time curve, and decreased the apparent total body clearance, renal clearance, urinary recovery of unchanged drug, and the excretion ratio (intrinsic renal clearance of AM-1155/creatinine clearance). This indicated that the tubular secretion contributed to the renal excretion of AM-1155. In the multiple-dose study, the concentrations of AM-1155 in serum and urine reached a steady state within 2 to 3 days. The measured concentrations in serum fitted well the simulation curve, which reflected the persistence of linear pharmacokinetics of AM-1155. In conclusion, AM-1155 is expected to be clinically useful because of its potent antibacterial activity and favorable pharmacokinetics.