Pharmacokinetics of Netilmicin in Patients with Renal Impairment and in Patients on Dialysis

Luft, Friedrich C.; Brannon, David R.; Stropes, Linda L.; Costello, Robert J.; Sloan, Richard G.; Maxwell, D. R.

doi:10.1128/aac.14.3.403

Cited by 28 publications

(9 citation statements)

References 10 publications

(17 reference statements)

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“…The terminal phase has a halflife of 198 h and is not correlated with creatinine clearance. The initial half-life differs from the value of 2.0 h reported for patients with normal renal function, but is consistent with the data of Luft et al (3), who estimated the netilmicin halflife at 5.1 h in patients with creatinine clearances of 45 to 70 ml/min and 2.7 h in patients with creatinine clearances of 70 to 100 ml/min. The terminal half-life was found to be 112 h. Wenk et al (16) calculated the half-life of this phase to be 39 h. This was a single-dose study, with serum sampling for 24 h and urine collections for only 72 h postdose.…”

Section: Discussionsupporting

confidence: 87%

Predicted tissue accumulation of netilmicin in patients

Edwards¹,

Mangione²,

Cumbo³

et al. 1981

Antimicrob Agents Chemother

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The two-compartment pharmacokinetics of netilmicin were investigated in 11 patients with stable renal function who were being treated for gram-negative infections. The initial dosage of netilmicin ranged from 2.5 to 5.0 mg/kg per day, with subsequent changes made on the basis of serum concentrations. Venous blood samples were obtained every 2 to 4 days during therapy and daily for an average of 10 days after the final dose. Serum concentrations were measured by both microbiological assay and radioimmunoassay. Peak and trough netilmicin concentrations were significantly greater (P < 0.01) at the end of therapy than at the first dose, even though renal function was stable throughout treatment in all patients. After the final dose, serum concentrations declined in a biphasic manner, with a first-phase half-life of 5.4 h and a terminal half-life of 198 h. The total body clearance averaged 31 ml/min. An average of 99 mg of netilmicin (approximately 5% of the total dose) was predicted to be in the tissue compartment at the end of therapy. A comparison of these pharmacokinetic parameters with those obtained in a previously reported but similar study with gentamicin showed no significant differences between the two aminoglycosides with respect to peak and trough concentrations (initially or at the end of therapy), volumes of distribution, total body clearance, or amount of drug in the tissue compartment at the end of therapy. The terminal half-life of netilmicin was significantly greater than that of gentamicin, whereas the rate constant of netilmicin for tissue influx (k12) was significantly less.

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Section: Discussionsupporting

confidence: 87%

Predicted tissue accumulation of netilmicin in patients

Edwards¹,

Mangione²,

Cumbo³

et al. 1981

Antimicrob Agents Chemother

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“…However, evidence of such nonrenal clearance has been provided by PK studies in anephric patients (26). The seminal studies from Schentag et al in the late 1970s clearly showed important aminoglycoside tissue accumulation in humans (33), and pharmacokinetic studies with prolonged serum and urine collections have shown a very prolonged terminal elimination phase and suggested that a threecompartment model better describes aminoglycoside elimination (39).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Four Renal Function Estimation Equations for Pharmacokinetic Modeling of Gentamicin in Geriatric Patients

Charhon

Neely²,

Bourguignon

et al. 2012

Antimicrob Agents Chemother

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“…The pharmacology of netilmicin is similar to that of gentamicin (9,14,25), but the alpha phase of netilmicin is more rapid than that of gentamicin (27), and higher doses (2 mg/kg per 8 h) have been recommended to achieve equivalent serum levels (9). Initial serum levels were predictable in only a small majority of our patients, although levels were less variable than gentamicin in another study (26).…”

Section: Resultsmentioning

confidence: 64%

Prospective comparative study of efficacy and toxicity of netilmicin and amikacin

Bock¹,

Edelstein²,

Meyer³

1980

Antimicrob Agents Chemother

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Eighty patients were treated with either amikacin or netilmicin in a prospective randomized study of serious gram-negative bacillary infections, including 11 due to gentamicin-resistant pathogens. Thirty-six treated with netilmicin and 35 treated with amikacin were evaluable for efficacy or toxicity, or both. The overall groups differed significantly only in age. There were no significant differences in efficacy of the two drugs. There were no statistically significant differences at the 95% level between the netilmicin group and the amikacin group with respect to nephrotoxic reactions (38 versus 28%, respectively) or ototoxic reactions (9 versus 25%, respectively). Further comparative trials of netilmicin and other aminoglycosides appear warranted before it is widely used.

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Pharmacokinetics of Netilmicin in Patients with Renal Impairment and in Patients on Dialysis

Cited by 28 publications

References 10 publications

Predicted tissue accumulation of netilmicin in patients

Predicted tissue accumulation of netilmicin in patients

Comparison of Four Renal Function Estimation Equations for Pharmacokinetic Modeling of Gentamicin in Geriatric Patients

Prospective comparative study of efficacy and toxicity of netilmicin and amikacin

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