Vol.58 No.S-2 October 2010
Pharmacokinetics and safety of oral tosufloxacin granule preparation in healthy adult subjects
1)Department of Research Project Studies, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan
2)Heishinkai Medical Group Osaka Pharmacology Clinical Research Hospital
Abstract
Development of quinolone antimicrobial agents for the use in children had been held back due to musculoskeletal disorder seen in juvenile animal studies. However, norfloxacin for the use in children was launched in the market in 1991 upon demand for effective oral antimicrobial agents against Pseudomonas aeruginosa and offending bacteria for enteric infection in medical practice.
Recently, increased cases of failure in treatment with oral β-lactam agents has been a serious problem owing to increase in the number of β-lactam- and macrolide-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae which are major offending bacteria for respiratory tract infection and otitis media in children. Due to high demand for drugs that can be used in out-patients for the treatment of resistant strains in medical practice, Japanese Society for Pediatric Infectious Disease recommended the Health, Labor and Welfare Ministry to discuss the use of tosufloxacin(TFLX) in children as it had been long used for the treatment of infections in adults demonstrating its safety and efficacy and its off-label use in children had been reported.
In this study, the pharmacokinetics and the safety of single doses of 100, 200, or 300 mg of active agent of TFLX granule were evaluated in healthy adult volunteers. The plasma drug concentration reached Cmax 2.4-2.6 hours after single oral doses of TFLX granule in average for each dose and T1/2 were 6.3-6.5 hours in average. The mean Cmax for 100, 200, and 300 mg doses was 0.54 μg/mL, 1.06 μg/mL, and 1.35 μg/mL. The mean AUC for the 100, 200, and 300 mg doses was 4.84 μg·h/mL, 9.99 μg·h/mL, and 12.69 μg·h/mL. The increase in Cmax and AUC was dose-dependent. The 24-hr urine excretion ratio after a 100, 200, or 300 mg dose was 49.7%, 43.1%, and 38.9%. Of 24 volunteers, 4 (16.7%) reported 6 adverse events. All of these events were mild and were not clinically significant.
This study for TFLX granule demonstrated a linear correlation between the plasma drug concentration and its dosage and its safe use with no clinically significant adverse events.
The TFLX granule preparation showed pharmacokinetics similar to those of the tablet promising similar efficacy as for the tablet. Furthermore, no specific adverse events were observed for the granule though this was a single dose study. Therefore, it is possible to conduct clinical trials in children with careful patient selection and with adequate attention to the drug concentration.
Key word
tosufloxacin, pharmacokinetics, safety
Received
May 10, 2010
Accepted
August 6, 2010
Jpn. J. Chemother. 58 (S-2): 24-31, 2010
