Vol.55 No.S-1 October 2007
Phase III study of garenoxacin in patients with secondary infection of chronic respiratory diseases
1)Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan
2)Department of Pharmacy, Keio University Hospital
3)Department of Respiratory Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University
(Present: Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University)
4)Department of Internal Medicine, Shinrakuen Hospital
5)Department of Allergy and Respiratory Diseases, Douai Memorial Hospital
(Present: Sano Toranomon Clinic)
6)Odagiri Respiratory Disease Clinic
7)Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School
(Present: Department of Clinical Infectious Diseases, School of Medicine, Showa University)
8)Second Department of Internal Medicine, Nagasaki University, School of Medicine
(Present: Division of Molecular and Clinical Microbiology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences)
9)First Department of Internal Medicine, School of Medicine, University of Ryukyus
(Present: Japanese Red Cross Nagasaki Genbaku Isahaya Hospital)
Abstract
The efficacy and safety of garenoxacin mesilate hydrate(GRNX), new oral des-fluoroquinolone antimicrobial, were investigated in patients with secondary infection occurred on chronic respiratory disorders. Patients were treated with GRNX 400 mg once daily for 10 days. Plasma concentration of GRNX in each patient was determined and the obtained clinical results were analysed based on pharmacokinetics(PK) and pharmacokinetics/pharmacodynamics(PK/PD) parameters.
Clinical efficacy rates were 87.8% (108/123) at the end of treatment and 83.7% (103/123) at the 7th day of post-treatment. Bacteriological eradication rates were 89.6% (60/67) and 85.1% (57/67) at the above time points. Eradication rates of causative organisms were 100% (13/13) in Streptococcus pneumoniae, 7/8 in Staphylococcus aureus, 100% (28/28) in Haemophilus influenzae and 8/8 in Moraxella (Branhamella) catarrhalis at the end of treatment. All penicillin-resistant S. pneumoniae(PRSP) including penicillin-intermediate resistant S. pneumoniae(PISP) were eradicated.
Drug-related adverse events were observed in 19 patients (26 events), the incidence rate was 14.0% (19/136). Gastrointestinal disorders including 4 cases of diarrhea (2.9%), 3 of loose stool (2.2%) and 3 of vomiting (2.2%) were frequently observed. Laboratory abnormalities were observed in 26 patients (19.3%). Frequent abnormalities were 14 cases of AST elevation (10.4%), 13 of ALT elevation (9.6%) and 5 of serum amylase elevation (3.8%). No relationship was observed between PK parameters (AUC0-24 and Cmax) and incidence of adverse events.
90.9% of patient in this study exceeded the target value of fAUC0-24/MIC>50. Clinical efficacy at the 7th day of post-treatment was 91.7% (55/60) in those cases whose target value was more than 50, but it was only 3/6 in those whose target value was less than 50. Similar results were obtained in studies in US and EU.
From aboves, it indicates that GRNX is a beneficial antimicrobial agent for secondary infection of chronic respiratory diseases.
Key word
garenoxacin, secondary infection of chronic respiratory disease, PK/PD analysis, population PK analysis
Received
July 5, 2007
Accepted
August 10, 2007
Jpn. J. Chemother. 55 (S-1): 144-161, 2007
