ro13-9904 and Carbon-Tetrachloride-Poisoning

Hepatopathy sometimes may interfere with metabolism and/or elimination of drugs which undergo major hepatic clearance. Twelve healthy goats were equally divided into two groups (I and II) and hepatopathy was induced by carbontetrachloride in the second group (group II). A single dose of ceftriaxone at 50 mg/kg was administered to each group intramuscularly. Disposition of ceftriaxone in plasma of healthy goats showed a typical absorption-reabsorption phase. However, the reabsorption phase was totally absent in hepatopathic goats and the disposition of ceftriaxone showed only absorption and distribution/elimination phase. The drug persisted in plasma for 6 h in hepatopathic animals, whereas the drug can only be detected up to 2 h in healthy animals indicating longer persistence of ceftriaxone in the former group. Ceftizoxime, the active metabolite of ceftriaxone was available in urine of group I animals, whereas only ceftriaxone was detected in the urine of hepatopathic animals suggesting impairment of metabolism of the parent drug in hepatopathy. Therefore, the reabsorption and metabolism of ceftriaxone in goats should be taken into consideration for drug monitoring.

Topics: Alanine Transaminase; Animals; Anti-Bacterial Agents; Area Under Curve; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Ceftriaxone; Chemical and Drug Induced Liver Injury; Female; Goats; Half-Life; Indicators and Reagents; Injections, Intramuscular; Liver Function Tests; Male; Sulfobromophthalein