Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers.

The common usage of extended spectrum beta-lactams co-administered with amikacin in everyday clinical practice for infections by multidrug-resistant isolates has created the need to search for pharmacokinetic interaction. Eighteen healthy volunteers were enrolled in the study; six were administered 1g of ceftazidime singly intravenously or combined with 0.5 g of amikacin; six received 0.5 g of imipenem singly or combined with 0.5 g of amikacin and six 1g of aztreonam singly or combined with 0.5 g of amikacin. Blood and urine samples were collected at regular time intervals and apparent serum levels were determined by a microbiological assay. Co-administration of ceftazidime and amikacin resulted in higher C(max) and AUC for amikacin than when administered alone. Co-administration of imipenem and amikacin resulted in higher C(max) for imipenem than when administered alone. The tested interactions did not affect plasma half-life (t(1/2)) and clearance rate of any antimicrobial compared with its single administration. All tested drugs were mainly eliminated by glomerular filtration. It is concluded that co-administration of ceftazidime, imipenem or aztreonam with amikacin in healthy volunteers might affect C(max) and AUC without influencing any other pharmacokinetic parameter. The probable clinical endpoint is that giving ceftazidime, imipenem or aztreonam with amikacin might result in a transient elevation of beta-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.

Pharmacokinetics of teicoplanin in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To achieve concentrations of teicoplanin in serum and dialysate within the therapeutic range in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Pharmacokinetic study. SETTING: A tertiary-care hospital. PATIENTS: Eight hospitalized anuric patients undergoing CAPD. INTERVENTIONS: One single dose of 10 mg/kg teicoplanin was administered intravenously, and blood and dialysate were sampled at regular time intervals for 48 hours post drug infusion. Concentrations of teicoplanin were determined by microbiological assay. RESULTS: Teicoplanin serum levels above 10 microg/mL, the level desired to treat systemic infections, were detected for 24 hours after administration. All dialysate concentrations were very low. Teicoplanin presented two phases of elimination: an early first phase and a late second phase. Mean maximum serum concentration was 75.56 microg/mL, mean half-life (t 1/2) of the early elimination was 3.34 hours, mean t 1/2 of the late elimination was 61.68 hours, mean area under the serum-concentration-time curve was 1491.92 mg x hr/L, mean clearance rate was 10.68 mL/ minute, mean apparent volume of distribution was 0.80 L/kg, and mean volume of distribution at steady state was 0.22 L/kg. Mean dialysate excretion was 3.16% and mean peritoneal clearance rate was 0.023 mL/minute. CONCLUSIONS: Based on the time period with the achieved serum levels and on the prolonged t 1/2, it is proposed that teicoplanin might be administered at 10 mg/kg every 24 hours for the therapy of systemic infections in patients undergoing CAPD. However, its intravenous administration should be avoided in the treatment of peritonitis, because the achieved dialysate concentrations were very low.

Pharmacokinetics of teicoplanin in patients undergoing chronic haemodialysis.

In order to define a dose regimen of teicoplanin for patients undergoing chronic haemodialysis so that they achieved trough drug serum levels above 10 mg/l, two single doses of 5 and 10 mg/kg were administered intravenously in seven anuric patients immediately after the end of haemodialysis. Concentrations of teicoplanin were determined by a microbiological assay in samples collected from peripheral veins via the arterial and the venous lines of the fistulae and from the dialysate during haemodialysis. The administration of a 5 and 10 mg/kg dose gave mean C(max) of 62.80 and 122.43 mg/l, mean AUC of 526.43 and 1103.98 mg h/l, mean half life (t(1/2)) of 109.09 and 107.06 h, mean clearance rates of 12.85 and 12.44 ml/min, mean apparent volumes of distribution of 1.68 and 1.68 l/kg and mean volumes of distribution at steady state of 0.31 and 0.28 l/kg, respectively. Trough serum levels above 10 mg/l were found for 24 h after the administration of the 5 mg/kg dose and for 48 h after the administration of the 10 mg/kg dose. Teicoplanin was not detected in the dialysate. Its concentrations in both the arterial and the venous lines of the fistulae were similar. Based on the time period after the administration of teicoplanin where the desired trough serum levels were found and on the observed t(1/2), it is proposed that teicoplanin should be administered at a dose of 10 mg/kg at 48-72 h intervals, in patients undergoing chronic haemodialysis for the therapy of infections caused by Gram-positive cocci.