General pharmacology of tazobactam/piperacillin (1):Effects on gross behavior, central nervous system, and respiratory and circulatory systems
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Tazobactam/piperacillin (TAZ/PIPC) is a 1:4 (weight) combination of tazobactam (TAZ), a new β-lactamase inhibitor, and piperacillin (PIPC). We investigated the effects of TAZ/PIPC given i.v. doses or <I>in vitro</I> on the central nervous system, respiratory system and circulatory system, and compared them with those of TAZ and PIPC alone. The following results were obtained.<BR>1. Gross behavior: TAZ/PIPC (up to 1600mg/kg), TAZ (up to 320mg/kg) and PIPC (up to 1280mg/kg) had no effect on gross behavior in mice.<BR>2. Central nervous system: TAZ/PIPC (up to 1600mg/kg), TAZ (up to 320mg/kg) and PIPC (up to 1280mg/kg) had no effect on spontaneous motor activity, motor coordination, hexobarbital sleeping time, convulsions induced by electroshock and pentetrazole, and stretching induced by acetic acid in mice, body temperature and conditioned avoidance response, spinal reflex in rats and spontaneous EEG activity in rabbits.<BR>3. Respiratory and circulatory systems: In anesthetized dogs, TAZ/PIPC decreased blood pressure and increased blood flow in doses above 800mg/kg. PIPC increased blood flow in doses above 320mg/kg and decreased blood pressure and heart rate in doses above 640mg/kg. TAZ had no effect on these parameters in doses up to 320mg/kg. None of the three drugs had any influence on isolated rabbit ear vessels or isolated guinea-pig atrium. The above results suggest that TAZ/PIPC does not significantly affect the central nervous system. The effects of TAZ/PIPC on the circulatory system are mainly caused by PIPC, and there is no interaction betweeen TAZ and PIPC.
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公益社団法人 日本化学療法学会 | 論文
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