Vol.55 No.S-1 October 2007
Phase 1 clinical studies of oral garenoxacin in healthy Japanese adult subjects
Department of Pharmacology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan
Abstract
Pharmacokinetic profiles, safety, and food effect of oral garenoxacin mesilate hydrate(GRNX), a novel des-F(6)-quinolone, were evaluated in studies with healthy Japanese adult subjects. The intrinsic ethnic factor of GRNX was investigated by reviewing comparison of pharmacokinetic parameters by Japanese with results of oversea studies.
1. Pharmacokinetics: In the single-dose study, linearity was shown between pharmacokinetic parameters (Cmax and AUC) and the GRNX dose. In the multiple-dose study, pharmacokinetic parameters come up to steady-state after dosing for 7 days, and accumulation was not observed. Cmax and AUC on day 7 were 11.06 μg/mL and 110.9 μg·h/mL.
2. Safety: No serious adverse events were observed in studies. GRNX was shown to be safe and well tolerated up to 600 mg single dose and 400 mg QD multiple-dose for 14 days. No relationship was noted between the ratio of adverse events and dosage or plasma concentration.
3. Effect of meals: The effect on pharmacokinetic parameters by fed or fasted administration was investigated at oral 400 mg dose. The fed/fasted ratio of geometric mean of Cmax and AUC were 0.876 and 0.925. The 90% confidential intervals for the ratios of the geometric mean of Cmax and AUC between fed and fasted were completely contained within the ranges specifying the absence of a food effect. The effect of meals was not found with GRNX.
4. Investigation of the intrinsic ethnic factor: Pharmacokinetic profiles of plasma concentration, metabolites, penetration to saliva, and ratio of protein-binding were investigated by comparing those with oversea studies. Pharmacokinetic profiles in Japanese were similar to results of oversea studies, and no intrinsic ethnic factor affected pharmacokinetic parameters of GRNX.
Key word
garenoxacin, T-3811MEa, des-fluoro(6)-quinolone, pharmacokinetic
Received
May 18, 2007
Accepted
July 19, 2007
Jpn. J. Chemother. 55 (S-1): 95-115, 2007
