Vol.58 No.5 September 2010
Phase I clinical study of high dose pazufloxacin in the healthy non-elderly and elderly subjects
Department of Infectious Diseases, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan
Abstract
High dose pazufloxacin(PZFX), an injectable fluoroquinolone antimicrobial, was administered to healthy non-elderly and elderly subjects to evaluate pharmacokinetics, safety, and tolerability in a single or multiple doses for a 60-minute drip infusion.
With 1% PZFX, single dose of 1,500 and 2,000 mg, and multiple doses of 1,000 mg twice daily for 5 days were performed. With already marketed 0.5% drug product, multiple doses of 1,000 mg twice daily for 6 days were evaluated in non-elderly and elderly subjects.
In single doses of 1,000, 1,500 and 2,000 mg, linearity was shown between pharmacokinetic parameter Cmax and dose, but was not between AUC and dose.
With intravenous 1,000 mg drip for 60 minute, AUC of the initial day were 59.42 μg·hr/mL in the healthy non-elderly subjects and 73.18 μg·hr/mL in those 65 years or older. Pharmacokinetic parameters reached the steady state on the day following administration, and accumulation was not observed.
During administration of 1,000 mg of 1% PZFX twice daily, adverse events frequency at the injection site was high, and some adverse events occurred in all subjects, so administering was discontinued two days after start. No serious adverse events were observed, but 1% PZFX was changed to 0.5% PZFX because all subjects discontinued.
When 1,000 mg of 0.5% PZFX was administered twice daily for 6 days, 5 adverse events (drug eruption, abnormal faeces, injection site erythema, and urinary sediment present) were observed in 4 of 8 non-elderly subjects. In elderly subjects, 16 adverse events (abnormal faeces, diarrhoea, injection site erythema, injection site pain, injection site phlebitis, injection site pruritus, and injection site urticaria) were observed in 5 of 10 subjects, but were mild or moderate and not clinically significant, indicating that PZFX was safe and well tolerated.
Above all findings, the safety of 1,000 mg of 0.5% PZFX twice daily for 6 days in non-elderly and elderly subjects was indicated.
Key word
pazufloxacin, high dose, pharmacokinetics
Received
June 1, 2010
Accepted
August 2, 2010
Jpn. J. Chemother. 58 (5): 560-577, 2010
