Pharmacokinetics of Cefpiramide in Rats Acutely Intoxicated with Carbon Tetrachloride

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Pharmacokinetics of cefpiramide (CPM) were investigated in normal rats and rats with hepatic intoxication induced by a single oral administration of carbon tetrachloride (CCl_4). The elimination half-life of the antibiotic was prolonged in CCl_4-intoxicated rats and the total body clearance in CCl_4-intoxicated rats (153.9 ml/h/kg) was about 40% of the control value (390.3 ml/h/kg), while the volume of distribution for CPM was scarcely affected. The hepatic clearance of CPM was markedly diminished and the renal clearance of CPM was slightly, but not significantly, decreased in CCl_4-intoxicated rats. It seems that the hepatic clearance of CPM was decreased owing to at least two factors ; (1) decrease in CPM uptake by hepatocytes and (2) decrease in bile flow, while the renal clearance of CPM was slightly decreased owing to decrease in the renal tubular secretion. These results suggest that CCl_4 intoxicates not only the liver but also the kidney to a small extent.
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