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Abstract:
The pharmacokinetic properties of ceftazidime were evaluated in laboratory animals. Peak serum concentrations following subcutaneous or intramuscular dosing of 25 mg/kg occurred 15-30 min after injection and ranged from 26 mg/l in mice to 63 mg/l in rabbits. Serum half-life values were 21 min in mice, 23 min in rats, 48 min in rabbits, 60 min in beagle dogs and 58 min in cynomolgus monkeys. Ceftazidime was not absorbed following oral dosing. Large amounts of unchanged ceftazidime were excreted in urine. Low biliary excretion, i.e. 1.2%, of subcutaneously administered ceftazidime was found in rats. This contrasted to high biliary excretion of cefmenoxime (20%), cefotiam (37.5%), moxalactam (40%) and cefoperazone (52%). The high intrinsic antibacterial activity of ceftazidime combined with good pharmacokinetics was reflected in excellent therapeutic effects in experimental infections. Ceftazidime was the most active of the newer beta-lactam antibiotics tested and only the aminoglycoside antibiotic gentamicin achieved the same level of activity. Ceftazidime, which is currently being assessed clinically, is a promising potential alternative to aminoglycoside antibiotics.