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Correlation between in vitro and in vivo models of proconvulsive activity with the carbapenem antibiotics, biapenem, imipenem/cilastatin and meropenem.
Toxicology Letters 1995 April
The present study evaluated the proconvulsant liability of biapenem, a novel carbapenem antibiotic, in in vitro and in vivo experiments, in comparison with the carbapenems, imipenem/cilastatin and meropenem. Imipenem/cilastatin is a carbapenem antibiotic with known proconvulsive liability in man and in animal experiments. In in vivo studies imipenem/cilastatin, at doses of 400/400 mg/kg i.v., significantly lowered the convulsive threshold of pentylenetetrazol (PTZ) in mice and shifted the dose-response curve of PTZ. The effects of biapenem (400 mg/kg i.v.) and another reference carbapenem, meropenem (400 mg/kg i.v.), in the mouse PTZ model were not significantly different from control. In in vitro experiments the carbapenems were tested for their ability to inhibit [3H]muscimol (1.3 mM) binding to rat brain homogenates at concentrations of 1-10 mM. Similar to in vivo results, when compared to imipenem/cilastatin, biapenem and meropenem did not inhibit [3H]muscimol binding to the GABAA receptor complex in brain homogenates while imipenem/cilastatin exhibited significant inhibition (IC50 = 4.6 mM). These results further confirm the correlation between in vitro GABAA binding and in vivo PTZ convulsive testing with carbapenem antibiotics, and suggest that biapenem possesses a low proconvulsive liability.
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