• Archives of Pharmacal Research
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• v.18 no.6
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• pp.423-426
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• 1995

SM-101 is a mixture of metampicillin and sulbactam(2:1). The antibacterial activities of SM-101 were compared with those of metampicillin, piperacillin and Augmentin. It showed powerful antibacterial activities against major strains. Except P. anruginosa and S. marcescens, the in vitro antibacterial activity of SM-101 was higher than those of metampicillin, piperacillin and Augmentin against Staphylococcus spp., Streptococcus spp., Moganella morganii, E. Coil, and Proteus spp. The $ED_{50}$ values of SM-101 were two-fold or greater than those of metampicillin, piperacillin and Augmentin against $\beta-lactamase$ producing strains, p. mirabilis GN79 and M. morganiii MB4-11. The in vivo efficacy of SM-101 was more active than metampicillin and pipeeracillin and similar to Augmentin against S. aureus Smith, E coli MB4-01 and K. pneumoniae MB4-02.

• Archives of Pharmacal Research
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• v.17 no.5
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• pp.378-380
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• 1994

The hydrolysis of metampicillin to ampicillin was investigated using high perofrmance liquid chromatography. We developed the simultaneous determination of metampicillin and ampicilin using a Zorbox CN column and 5% acetonitrile and 8% methanol in 0.02 M phosphate buffer (pH 7.0) as mobile phase. Matampicillin was hdyrolyzed to ampicillin with half life of 41.5 min at physiological pH and temperature. In acdic pH, metampicillin was rapidly hydrolyzed to ampicillin within a chromatogrphic separation.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.51-58
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• 1996

A new composite antibiotic, SM-101(sulbactam.metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to Sprague-Dawley male rats from predating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. In male parents, two deaths occurred at 1000 mg/kg. The increase in kidney weight of the 1000 mg/kg group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 mg/kg. The decrease in spleen weight were seen at 250, 500 and 1000 mg/kg. In female parents, three deaths were found at 1000 mg/kg. Mating performance and fertility of parent animals were not adversely affected by all doses tested. F1 fetuses showed no changes related to treatment of SM-101. The results show that the no effect dose level(NOEL) for general toxicity of parent animals is under 250 mg/kg/day and NOELS for reproductive capability and fatal development are over 1000 mg/kg/day.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.59-67
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• 1996

A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 375, 750 and 1500 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. In dams, two deaths occurred at 375 and 1500 mg/kg, respectively. The decrease in the weight of adrenal glands of the 1500 mg/kg group was observed. The prolongation of pregnancy period was found at 1500 mg/kg. F1 fetuses showed no changes related to the treatment of SM-101. In F1 offspring, the increase in spleen weight was seen at all doses treated. No treatment-related abnormalities were observed in each treated group in terms of development, behaviour and reproductive performance. In F2 fetuses, no drug-induced abnormalities occurred at all doses. The results show that the no-effect dose levels (NOELS) for dams and Fl offspring are under 375 mg/kg/day and NOELs for F1/F2 fetuses are over 1500 mg/kg/day.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.339-348
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• 1996

A new composite antibiotic, SM-101 (sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on dams and growth, behaviour and mating performance of Fl offspring were examined. In dams, one death occurred at 1000 mg/kg. The increase in kidney weight of the 250, 500 and 1000 mg/kg group was found. In F1 offspring, both delayed incisors eruption and decreased body weight were observed in females of the 1000 mg/kg group. The increase in the weights of liver and kidney was found in males of the 1000 mg/kg group. No treatment-related abnormalities were observed in each treated group in terms of behaviour and reproductive performance. In F1/F2 fetuses, no drug-induced abnormalities occurred at all doses tested. The results show that the no effect dose level (NOEL) of SM-101 is under 250 mg/kg/day for dams and 500 mg/kg/day for F1 offspring, and over 1000 mg/kg/day for F1/F2 fetuses.