Pharmacokinetics of Amikacin for Treatment of Urinary Tract Infections in Patients with Reduced Renal Function

Abstract

Amikacin (250 mg four times daily for 10 days) was administered intramuscularly to 22 patients with long-standing, severe infections of the urinary tract, in each case superimposed on chronic uropathy or nephropathy. Therapy with amikacin was completely successful in 14 patients (sterile 14-day follow-up urine specimens obtained by suprapubic needle aspiration of the bladder) and partially successful in three (sterile three-day but positive 14-day follow-up urine specimens). Five patients were judged to be treatment failures. Quantitative assessment of pyuria revealed a significant drop in the rate of excretion of white cells to near normal levels not only in patients who were cured but also in others, a finding which suggests that the infectious process had been affected by amikacin in all cases. The course of the disease in individual patients suggested that amikacin therapy can be successful after a long series of failures from treatment of such conditions with other antibiotics. Additional pharmacokinetic studies indicated that the half-life of amikacin may be increased five- to 10-fold in patients with renal insufficiency. A tentative dosage schedule was prepared for patients with various degrees of impaired renal function on the basis of average half-life values.

Pharmacokinetics of amikacin in hematologic malignancies

“…The volume of distribution reported previously for adults varied from approximately 0.17 + 0.06 liters/kg (5) to 0.29 + 0.058 liters/kg (2) and is considerably less than the volume of distribution of 0.39 ± 0.16 liters/kg obtained in this study. The total body clearance in our study of 2.08 ml/min per kg, or 121.59 ml/min per 1.73 m2, is within the range of 78.6 to 129.7 ml/min per 1.73 m2 reported by others (12).…”

Amikacin pharmacokinetics in pediatric patients with malignancy

“…Studies of pharmacokinetic properties of amikacin in adults have shown the volume of distribution to be 0.25 liter/kg, which is similar to the Vd we found (3,4,6,11,16,18). A previous study of amikacin in pediatric patients revealed a Vd of 0.32 liter/kg, but this higher value probably was due to the inclusion of a large number of patients with cystic fibrosis, who have abnormal weight-to-surface area ratios (25).…”

“…A previous study of amikacin in pediatric patients revealed a Vd of 0.32 liter/kg, but this higher value probably was due to the inclusion of a large number of patients with cystic fibrosis, who have abnormal weight-to-surface area ratios (25). The differences in the clinical pharmacology between our pediatric patients and adults can be accounted for by the significantly greater total body clearance of amikacin (131 versus 100 ml/min per 1.73 m2) and shorter half-life (1.24 h in children versus 2.2 h in adults) (3,4,6,11,16,18).…”

“…It is effective in the treatment of patients with serious infections due to gram-negative bacilli and is particularly useful in therapy of infections involving organisms that are resistant to other aminoglycoside antibiotics (1,21). Pharmacokinetic data related to its use in adults (3,4,6,11,16,18) and neonates (5,12,22) are available; however, infornation supporting the recommended dose and frequency ofadministration for older infants and children is scant (15,25). We evaluated pharmacokinetic parameters and toxicity in 50 pediatric patients who ,ug/ml for group I; 18.1 ± 3.2 lAg/ml for group II; and 17.2 + 1.7 ug/ml for group IH.…”

Pharmacokinetics of intravenous amikacin after rapid and slow infusion with special reference to hemodialysis

“…half-life and creatinine clearance (6,9,10), as well as between amikacin half-life and serum creatinine concentration (11,12) have been established. Finally, the pharmacokinetics of arnikacin during hemodialysis (13,14,15) and peritoneal dialysis (13,15) were examined.…”