title: Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.
abstract: 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, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. 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 was 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.
authors.affiliation: Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, Welwyn, Hertfordshire, United Kingdom. Ann-Allen/DEV/PHRD/SB_PLC@SB_PHARM_RD.com
authors.forename: A
authors.initials: A
authors.lastname: Allen
authors.forename: E
authors.initials: E
authors.lastname: Bygate
authors.forename: S
authors.initials: S
authors.lastname: Oliver
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.forename: A J
authors.initials: AJ
authors.lastname: Cheon
authors.forename: Y S
authors.initials: YS
authors.lastname: Choo
authors.forename: I C
authors.initials: IC
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D006801:Humans; D008297:Male; D009287:Naphthyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D011247:Pregnancy
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D000077735:Gemifloxacin