Pharmacokinetics of Amikacin in Patients with Renal Insufficiency: Relation of Half-Life and Creatinine Clearance

Pijck, J.; Hallynck, Th.; Soep, H.; Baert, Lieven; Daneels, R; Boelaert, Johan R.

doi:10.1093/infdis/135.supplement_2.s331

Cited by 27 publications

(8 citation statements)

References 6 publications

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“…Similar to other aminoglycosides, amikacin is primarily excreted through the kidney where it undergoes mainly glomerular ® ltration and slight tubular reabsorption (Clarke et al 1974). In subjects with normal and impaired renal function, a linear relationship between levels of creatinine in serum and elimination parameters of amikacin has been reported (Pijck et al 1976;Sarubbi & Hull 1978;Elting et al 1990). Elting et al (1990) documented that amikacin paralleled the daily changes in kidney function measured by urine volume and glomerular ® ltration rate.…”

Section: Discussionmentioning

confidence: 97%

“…Conversely, higher levels were seen in the early morning, following the night-time decrease in renal function, and thus, clearance of amikacin. As amikacin is excreted via the urinary tract, the need to modify amikacin dosage for patients with impaired renal function has been pointed out, since in those patients accumulation of the drug was observed (Pijck et al 1976;Lanao et al 1981;Vanhaeverbeek et al 1993).…”

Section: Discussionmentioning

confidence: 99%

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Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans

Droździk

Domański

Wójcicki

et al. 2002

Journal of Pharmacy and Pharmacology

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As unilateral nephrectomy is not a rare surgical procedure, it gives rise to the question whether drugs predominantly eliminated through the urinary tract can be handled effectively by the remaining kidney. Amikacin is predominantly excreted via glomerular filtration with only a small fraction undergoing tubular reabsorption, and can be used as a model drug of glomerular elimination. The study was carried out in 28 subjects, 10 one month and 10 one year after unilateral nephrectomy, as well as in 8 healthy subjects. The pharmacokinetics of amikacin was investigated after a 1-h infusion of 5 mg kg(-1) amikacin. Blood samples were collected for 24 h after the end of infusion. Pharmacokinetic parameters of amikacin were calculated using a one-compartment open model for intravenous administration. Amikacin concentrations were significantly elevated in nephrectomized patients as compared with control subjects, both 1 month and 1 year after the surgery, and were similar at these two time-points following unilateral nephrectomy. Pharmacokinetic parameters of amikacin in patients subjected to unilateral nephrectomy were significantly different from those observed in the control subjects. As compared with the controls, an increase in AUC (area under the serum concentration-time curve) by 81% (P < 0.001) and 63% (P < 0.01) 1 month and 1 year after nephrectomy was observed, respectively. The lambda(z) (elimination rate constant) was reduced by 39% (P < 0.001) after 1 month and by 38% (P < 0.001) 1 year after the operation and t 1/2 was prolonged by 70% (P < 0.001) and by 43% (P < 0.01) at the respective time-points following unilateral nephrectomy. CLT (total body clearance of the drug from plasma) and CL(BW) (clearance per kg body weight) were both significantly decreased in unilaterally nephrectomized subjects in comparison with the controls. CLT and CL(BW) were reduced by 53% (P < 0.001) and 42% (P < 0.01) 1 month after nephrectomy, and by 45% (P<0.001) and 42% (P<0.01) 1 year after the surgery, respectively. No significant differences among studied groups were found in C0 (initial serum drug concentration) and Vd (apparent volume of distribution). The results suggest that unilateral nephrectomy impairs elimination of amikacin, and possibly other drugs predominantly eliminated via glomerular filtration.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans

Droździk

Domański

Wójcicki

et al. 2002

Journal of Pharmacy and Pharmacology

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“…Ligation of the ureters causes similar modifications in the behavior of gentamicin [21]. Thus, under such conditions, it is impor tant to make a scrupulous adjustment of the dosage, taking into account the cessation or reduction of renal function [23],…”

Section: A--------------a Gentamicinmentioning

confidence: 99%

Behavior of Amikacin in Renal Parenchyma of Normal Rats and of Rats with Acute Obstructive Renal Insufficiency

Rudhardt¹,

Fabre²

1979

Nephron

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Aminoglycosides show a remarkable tendency to accumulate and persist in the renal parenchyma. In order to study the kinetics of this phenomenon for amikacin, rats received 25 mg/kg of this antibiotic i.p. and were sacrificed in groups of 6 up to 15 days after the injection. At 6 h, while the other organs and the serum were almost completely freed of amikacin, concentrations in the renal cortex reached 156 ± 21 µg/g, or 6 times the peak serum level (instead of 20 times the peak serum level for gentamicin or sisomicin, a difference which is reduced by the fact that amikacin is given in higher dosage). They then decreased very slowly, according to a half-life of 122 h. Although it decreases glomerular filtration, ligation of ureters 20 h before the injection quadrupled the concentration in the cortex. These data explain the characteristics of the nephrotoxicity of amikacin and the increased toxic risk in acute obstructive renal insufficiency.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Pechère

Dugal

Pechere

1979

European Journal of Drug Metabolism and Pharmacokinetics

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The pharmacokinetics of amikacin, a recently introduced aminoglycoside structurally related to kanamycin, were determined in healthy volunteers after rapid and slow constant-rate intravenous administration of a 7.5 mg/kg dose. The elimination profile of amikacin can be described by two compartment open model kinetics. Peripheral distribution of the drug is extremely rapid, and beta-phase concentrations decay with a half-life averaging about 2 hours, while inter-compartmental equilibrium is achieved in a little over 30 minutes. The volume of distribution averages about 25% of body weight. During hemodialysis, amikacin extraction from the blood reaches 97% +/- 17% (mean +/- 95% confidence interval) that of creatinine and 89% +/- 20% that of blood urea nitrogen. A method of administration adapted to the kinetic properties of the antibiotic is proposed.

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Pharmacokinetics of Amikacin in Patients with Renal Insufficiency: Relation of Half-Life and Creatinine Clearance

Cited by 27 publications

References 6 publications

Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans

Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans

Behavior of Amikacin in Renal Parenchyma of Normal Rats and of Rats with Acute Obstructive Renal Insufficiency

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

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