The pharmacokinetics of ceftazidime were studied in 18 male individuals, including six healthy volunteers and 12 patients with liver cirrhosis and ascites. Each participant received 1 g of ceftazidime as a single intravenous bolus injection. The elimination half-life was longer in cirrhotic than in control patients (5.40 +/- 1.02 h) vs. (1.98 +/- 0.24 h), P less than 0.01; probably due to slow return from the ascitic compartment. Nevertheless, total body clearance did not differ significantly between the two groups (81.4 +/- 30.3 ml/h/kg vs. 83.6 +/- 24.9 ml/h/kg). Dose reduction is not necessary when treating systemic infection in cirrhotics. Ceftazidime attained a concentration of 1 microgram/ml in the ascitic fluid in most patients 15 to 30 min after the injection, and maintained this level, which is higher than the MIC90 of Enterobacteriaceae, for 24 h. An intravenous bolus injection of 1 g ceftazidime every 24 h is sufficient to treat patients with spontaneous bacterial peritonitis caused by a susceptible organism other than Pseudomonas aeruginosa.
The pharmacokinetics of cefodizime (HR 221) were studied in 6 healthy male individuals and 12 male patients with various degrees of chronic renal failure following intravenous bolus injection of 1 g of the drug. Serum pharmacokinetics were described by an open two-compartment kinetic model. The serum levels of cefodizime exceeded the MIC90 for Enterobacteriaceae, Haemophilus influenzae and Neisseria gonorrhoeae for more than 12 h in healthy individuals and 24 h in renal failure patients. The half-life of elimination was significantly prolonged (p < 0.001) from 2.7 ± 0.2 h in healthy volunteers to 7.7 ± 1.5 h in renal failure patients. The total systemic clearance decreased significantly (p < 0.001) from 43.3 ± 5.8 ml/h/kg in healthy volunteers to 23.2 ± 5.6 ml/h/kg in renal failure patients. A linear correlation (r = 0.9; p < 0.001) was found between creatinine clearance and the total systemic clearance of cefodizime. The AUC0–∞ in patients with renal failure was more than double the value in healthy volunteers. An equation to calculate the 1-gram dose interval of cefodizime in patients with compromised renal function is provided.
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