Pharmacokinetics of Netilmicin in Renal Insufficiency and Haemodialysis

Abstract

The pharmacokinetics of intravenously administered netilmicin, an investigational aminoglycoside antibiotic, were studied in 38 patients with creatinine clearance ranging from 150 to Oml/min/1.73m2 in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum disappearance of netilmicin followed first order kinetics and the elimination rate constant decreased proportionally with decreasing renal function. Half-lives averaged 2.2 hours in normal individuals (creatinine clearance greater than 80ml/min/1.73m2) and reached 42 +/- 10 hours (mean +/- SD) in virtually anephric patients. The elimination rate constant lowered proportionally with decreasing renal function. Several linear relationships between pharmacokinetic parameters and renal function indicators were defined. A clinically useful correlation indicates that the half-life may be approximated as 3 times the serum creatinine concentration and may be used for adjustment of dosage of netilmicin in the treatment of patients with impaired renal function. During haemodialysis, netilmicin extraction from the blood reaches 75 +/- 14% (mean +-/ 95% confidence interval) of that of creatinine and 88 +/- 19% of that of blood urea nitrogen.

Gentamicin pharmacokinetic changes in induced acute canine nephrotoxic glomerulonephritis

“…Altered volume of distribution could partially explain the unpredictability of gentamicin serum concentrations observed by various investigators (1,2,14,25). As reported previously, aminoglycoside volume of distribution was increased in some patients with renal insufficiency (12,23,30). Gill and Kern reported an increase in volume of distribution of gentamicin in ascitic patients (10).…”

“…An increased volume of distribution has been reported in some studies of aminoglycoside dis-position in patients with renal insufficiency (12,23,30). In addition, volume of distribution varied widely in surgical patients with normal renal function (34).…”

Netilmicin Sulfate: A Comparative Evaluation of Antimicrobial Activity, Pharmacokinetics, Adverse Reactions and Clinical Efficacy

“…Most of the remaining netilmicin, as with other aminoglycosides, is slowly. excreted in the urine with a terminal or y-phase halflife ranging from 33-432 h o u r~.~~-~~ In subjects with renal impairment, there are linear relationships between: (1) the p or elimination-rate constant and the endogenous creatinine clearance, and (2) the serum half-life and the serum creatinine on cent ration.^^, [54][55][56] From these relationships, the half-life of netilmicin can be roughly estimated by multiplying the steady-state serum creatinine by 3 or dividing 230 by the creatinine clearance.5556 Observed serum half-lives in patients with creatinine clearances less than 10 mlimin have ranged from 24-42 h o u r~.~~-~~ Peak and mean urine concentrations of netilmicin are also dependent on the degree of renal function and have varied from 12-800 pgiml VOLUME 3, NUMBER 6, NOVEMBER~DECEMBER 1983 in patients with creatinine clearance of 18 mlimin or higher.6&62a…”

“…In adults, the apparent volume of distribution of netilmicin is about 20-30% of body weight, which corresponds with the extracellular fluid v~l u m e .~~-~~ Slightly higher values have been reported in renal failure. 46,[55][56] In neonates, the volume of distribution is 47-68% of body eight;^'-^^ older children exhibit values approaching those observed in adults. As netilmicin is not significantly bound by serum proteins, one would expect excellent penetration into interstitial fluid.…”

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

“…A: amikacin CR: creatinine and BUN: blood urea nitrogen. Table 3 Extraction of amikacin, creatinine and bun over a six-hour hemodialysis period This extraction is somewhat slower than that found by us with tobramycin (27) and sisomicin (28) but of the same order of magnitude than that· of netilmicin (29). Therefore, the amikacin serum concentration decay during an hemodialysis procedure can be predicted, with a clinically acceptable error, from BUN and/or creatinine measurements over that period.…”