Multiple-dose pharmacokinetics of amikacin and ceftazidime in critically ill patients with septic multiple-organ failure during intermittent hemofiltration

Abstract

The pharmacokinetic parameters of amikacin and ceftazidime were assessed in four patients undergoing hemofiltration for septic shock. The parameters were assessed during hemofiltration and in the interim period. The concentration-time profiles of these two drugs in plasma, urine, and ultrafiltrate were investigated after intravenous perfusion (30 min). In all cases a 1-g dose of ceftazidime was administered; for amikacin, the dosage regimen was adjusted according to the patient's amikacin levels (250 to 750 mg). Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection for ceftazidime and by enzyme multiplied immunoassay for amikacin. The elimination half-life (tl2) and the total clearance of amikacin ranged from 31.1 to 138.2 h and from 5.4 to 8.9 ml/min, respectively, during the interhemofiltration period in anuric patients. Hemofiltration substantially decreased the tl12 (3.5 0.49 h) and increased the total clearance (89.5 + 11.8 ml/min). The hemofiltration clearance of amikacin represented 71% of the total clearance, and the hemofiltration process removed, on average, 60% of the dose. During hemofiltration, the elimination t112 of ceftazidime (2.8 + 0.69 h) was greatly reduced and the total clearance increased (74.2 11.2 ml/min) compared with those in the interhemofiltration period (9 to 43.7 h and 7.4 to 16.8 ml/min, respectively). About 55% of the administered dose was recovered in the filtrate, and the hemofiltration clearance of ceftazidime was 46 + 14.3 ml/min. A redistribution phenomenon (rebound) in the amikacin and ceftazidime concentrations in plasma (35 and 28%, respectively) was reported after hemofiltration in two patients. The MICs for 90%o of the most important pathogens were exceeded by the concentrations of the two drugs in plasma during the whole treatment of these patients.

Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy

“…In previous studies with intensive care unit (ICU) patients undergoing CRRT, amikacin clearance varied from 0.53 to 5.34 liters/h, accounting for 40 to 89% of the total body clearance (10)(11)(12)(13)(14)(15). These studies also reported conflicting results on the correlation between drug clearance and CRRT settings (11,14).…”

Pharmacokinetic‐pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis

“…Previous studies of ceftazidime pharmacokinetics in severely ill patients show a wide variation in estimated clearance and volume of distribution [31–33] although in every study, including the present one, renal function remains the major determinant of ceftazidime clearance. The pharmacokinetic properties of ceftazidime in Thai patients with septicaemic melioidosis were similar to those reported previously in patients with other causes of shock and renal failure.…”

Implication of Haemodiafiltration Flow Rate on Amikacin Pharmacokinetic Parameters in Critically Ill Patients

“…D’Arcy et al [27] concluded that the use of extra renal clearance procedures could lead to an increase in the gentamicin clearance of between 10 and 40 mL/min in addition to the corresponding clearance for the same patients without renal replacement therapy. On the other hand, it has been established that the plasma half-life of the drug in patients with haemodiafiltration is much lower in patients with renal failure who are not submitted to these procedures [28]. However, the information available on the effect of the flow of the CVVHDF technique on concentrations reached by amikacin is still limited.…”