Pharmacokinetics of ceftazidime in patients with liver cirrhosis and ascites.

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.

Pharmacokinetics of cefodizime in normal individuals and in patients with renal failure.

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 less than 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 less than 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 less than 0.001) was found between creatinine clearance and the total systemic clearance of cefodizime. The AUC0-infinity 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.

Single-dose pharmacokinetics of aztreonam in healthy volunteers and renal failure patients.

The pharmacokinetics of aztreonam were studied in 6 healthy male volunteers and 12 male patients with various degrees of chronic renal failure after intravenous bolus injection of 1g of the drug. Serum pharmacokinetics of aztreonam were described by an open, two-compartment kinetic model. The serum levels of aztreonam exceeded the reported minimum inhibitory concentration (MIC)90 for Enterobacteriaceae for 8 hours and up to 24 hours, in healthy volunteers and renal failure patients, respectively. However, the serum levels of the drug exceeded the MIC50 for Pseudomonas aeruginosa for only 4 hours and 12 hours in healthy volunteers and patients, respectively. The half-life of elimination (t 1/2/beta) increased significantly (P less than 0.001) from 1.8 +/- 0.14 h in healthy volunteers and to 4.9 +/- 1.1 h in patients with renal failure. The total serum clearance of aztreonam decreased significantly (P less than 0.001) from 84.2 +/- 7.8 ml/h/kg in healthy volunteers to 30.2 + 9.2 ml/h/kg in patients with renal failure. A linear correlation (r = 0.971, P less than 0.001) was found between creatinine clearance and the total serum clearance of aztreonam. The AUC0-infinity increased significantly (P less than 0.001) from 137.5 +/- 12.2 micrograms/h/ml in healthy volunteers to 464 +/- 114.5 micrograms/h/ml in patients with renal failure.