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Antimicrobial Agents and Chemotherapy, June 2000, p. 1604-1608, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Pharmacokinetics and Tolerability of Gemifloxacin (SB-265805) after Administration of Single Oral Doses to Healthy Volunteers

Ann Allen,1,* Elizabeth Bygate,2 Stuart Oliver,3 Martin Johnson,3 Christopher Ward,3 Ae-Jin Cheon,4 Youn Sung Choo,4 and In-Chull Kim5

Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, Welwyn, Hertfordshire,1 Clinical Pharmacology Department, SmithKline Beecham Pharmaceuticals, Harlow, Essex,2 and Covance, Leeds,3 United Kingdom, and Clinical Drug Development4 and Drug Evaluation and Development,5 Biotech Research Institute, LG Chemicals Research Park, Taejon, South Korea

Received 12 October 1999/Returned for modification 16 January 2000/Accepted 24 March 2000

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 (Cmax) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of Cmax and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC0-infinity ) increased linearly with dose. Serum AUC0-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 µg · 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.

* Corresponding author. Mailing address: Pharmacokinetics Department, SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn, Herts AL6 9AR, United Kingdom. Phone: 01438-782598. Fax: 01438-782600. E-mail: Ann_Allen/DEV/PHRD/SB_PLC{at}SB_PHARM_RD.com.

Antimicrobial Agents and Chemotherapy, June 2000, p. 1604-1608, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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