Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers

被引:58
作者
Allen, A
Bygate, E
Oliver, S
Johnson, M
Ward, C
Cheon, AJ
Choo, YS
Kim, IC
机构
[1] SmithKline Beecham Pharmaceut, Dept Clin Pharmacol, Welwyn Garden City AL6 9AR, Herts, England
[2] Covance, Leeds, W Yorkshire, England
[3] SmithKline Beecham Pharmaceut, Drug Metab & Pharmacokinet, Welwyn Garden City AL6 9AR, Herts, England
[4] Biotech Res Labs Inc, Clin Drug Dev, Taejon, South Korea
[5] Biotech Res Labs Inc, Drug Evaluat & Dev, Taejon, South Korea
关键词
D O I
10.1128/AAC.44.6.1604-1608.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C-max) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C-max and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65 +/- 0.01, 1.28 +/- 0.22, 2.53 +/- 0.31, 5.48 +/- 1.24, 9.82 +/- 2.70, 24.4 +/- 7.1, and 31.4 +/- 7.6 mu g h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4 +/- 2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose ri;as excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.
引用
收藏
页码:1604 / 1608
页数:5
相关论文
共 6 条
[1]   Antimicrobial activity and spectrum of LB20304, a novel fluoronaphthyridone [J].
Cormican, MG ;
Jones, RN .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (01) :204-211
[2]  
ERWIN ME, 1999, QUALITY CONTROL STUD, V37, P279
[3]  
Gibaldi M., 1982, PHARMACOKINETICS, P45
[4]  
Hohl Annik F., 1998, Clin Microbiol Infect, V4, P280
[5]   Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines [J].
Johnson, DM ;
Jones, RN ;
Erwin, ME .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1999, 33 (02) :87-91
[6]   In vitro and in vivo evaluations of LB20304, a new fluoronaphthyridone [J].
Oh, JI ;
Paek, KS ;
Ahn, MJ ;
Kim, MY ;
Hong, CY ;
Kim, IC ;
Kwak, JH .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (06) :1564-1568