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. 1981 Dec;20(6):714–717. doi: 10.1128/aac.20.6.714

Predicted tissue accumulation of netilmicin in patients.

D J Edwards, A Mangione, T J Cumbo, J J Schentag
PMCID: PMC181787  PMID: 7325637

Abstract

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 less than 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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chung M., Costello R., Symchowicz S. Comparison of netilmicin and gentamicin pharmacokinetics in humans. Antimicrob Agents Chemother. 1980 Feb;17(2):184–187. doi: 10.1128/aac.17.2.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Jahre J. A., Fu K. P., Neu H. C. Kinetics of netilmicin and gentamicin. Clin Pharmacol Ther. 1978 May;23(5):591–597. doi: 10.1002/cpt1978235591. [DOI] [PubMed] [Google Scholar]
  3. Luft F. C., Brannon D. R., Stropes L. L., Costello R. J., Sloan R. S., Maxwell D. R. Pharmacokinetics of netilmicin in patients with renal impairment and in patients on dialysis. Antimicrob Agents Chemother. 1978 Sep;14(3):403–407. doi: 10.1128/aac.14.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Luft F. C., Yum M. N., Kleit S. A. Comparative nephrotoxicities of netilmicin and gentamicin in rats. Antimicrob Agents Chemother. 1976 Nov;10(5):845–849. doi: 10.1128/aac.10.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Meyers B. R., Hirschman S. Z. Antimicrobial activity in vitro of netilmicin and comparison with sisomicin, gentamicin, and tobramycin. Antimicrob Agents Chemother. 1977 Jan;11(1):118–121. doi: 10.1128/aac.11.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Meyers B. R., Hirschman S. Z., Wormser G., Siegel D. Pharmacokinetic study of netilmicin. Antimicrob Agents Chemother. 1977 Jul;12(1):122–123. doi: 10.1128/aac.12.1.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Regamey C., Gordon R. C., Kirby W. M. Comparative pharmacokinetics of tobramycin and gentamicin. Clin Pharmacol Ther. 1973 May-Jun;14(3):396–403. doi: 10.1002/cpt1973143396. [DOI] [PubMed] [Google Scholar]
  8. Riff L. J., Moreschi G. Netilmicin and gentamicin: comparative pharmacology in humans. Antimicrob Agents Chemother. 1977 Apr;11(4):609–614. doi: 10.1128/aac.11.4.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Schentag J. J., Cumbo T. J., Jusko W. J., Plaut M. E. Gentamicin tissue accumulation and nephrotoxic reactions. JAMA. 1978 Nov 3;240(19):2067–2069. [PubMed] [Google Scholar]
  10. Schentag J. J., Jusko W. J., Plaut M. E., Cumbo T. J., Vance J. W., Abrutyn E. Tissue persistence of gentamicin in man. JAMA. 1977 Jul 25;238(4):327–329. [PubMed] [Google Scholar]
  11. Schentag J. J., Lasezkay G., Cumbo T. J., Plaut M. E., Jusko W. J. Accumulation pharmacokinetics of tobramycin. Antimicrob Agents Chemother. 1978 Apr;13(4):649–656. doi: 10.1128/aac.13.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schentag J. J., Plaut M. E., Cerra F. B. Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients. Antimicrob Agents Chemother. 1981 May;19(5):859–866. doi: 10.1128/aac.19.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Siersbaek-Nielsen K., Hansen J. M., Kampmann J., Kristensen M. Rapid evaluation of creatinine clearance. Lancet. 1971 May 29;1(7709):1133–1134. doi: 10.1016/s0140-6736(71)91873-3. [DOI] [PubMed] [Google Scholar]
  14. Smith C. R., Lipsky J. J., Laskin O. L., Hellmann D. B., Mellits E. D., Longstreth J., Lietman P. S. Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980 May 15;302(20):1106–1109. doi: 10.1056/NEJM198005153022002. [DOI] [PubMed] [Google Scholar]
  15. Wenk M., Spring P., Vozeh S., Follath F. Multicompartment pharmacokinetics of netilmicin. Eur J Clin Pharmacol. 1979 Nov;16(5):331–334. doi: 10.1007/BF00605631. [DOI] [PubMed] [Google Scholar]

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