[Evaluation of once-daily administration of arbekacin. Experimental study and determination of pharmacokinetic properties in man].
Experimental and phase I clinical studies were performed to evaluate the efficacy and safety of once-daily administration of arbekacin (ABK). The results obtained were as follows: 1. ABK displayed dose-dependent, excellent antibacterial activity and post-antibiotic effects (PAE) against MRSA. 2. No significant difference was found between once-daily and divided administration regimens in protection against an experimental MRSA infection in mice. 3. There was no significant difference between once-daily and twice-daily administration of ABK in ototoxicity in guinea pigs or in nephrotoxicity in rats. 4. In the phase I clinical study using 200 mg single daily administration of ABK, no abnormal laboratory test results or symptoms were observed. 5. In the phase I clinical study of 5-day repeated administration of 200 mg/day of ABK, headache and increase in WBC sediment in the urine was noted in 1 volunteer; however these were not confirmed to be attributable to ABK. No abnormal laboratory test results were obtained other than increases in beta 2-microglobulin, NAG and gamma-GTP levels, each of which returned to normal after the completion of ABK administration. No abnormality was observed in the audiometry examination. 6. Maximum serum concentration (Cmax), serum half-life (T1/2 beta) and urinary recovery rate (0-48 hours) after single administration of 200 mg of ABK, were 13.20 micrograms/ml, 2.30 hours and 86.75%, respectively. There were no significant differences in pharmacokinetic parameters or urinary recovery rates between day 1 and day 5 in the 5-day repeated administration study. These findings suggest that once-daily administration regimen of ABK may be as effective and safe as divided administration regimen for the treatment of MRSA infection. Further clinical evaluation is required, however.
Totsuka
K
K
Department of Internal Medicine, Tokyo Women's Medical College.
Shimizu
K
K
Mitomi
N
N
Niizato
T
T
Araake
M
M
D000328:Adult; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents; D003982:Dibekacin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006168:Guinea Pigs; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D003982:Dibekacin; C031986:arbekacin