European Journal of Clinical Pharmacology

, Volume 16, Issue 5, pp 331–334 | Cite as

Multicompartment pharmacokinetics of netilmicin

  • M. Wenk
  • P. Spring
  • S. Vozeh
  • F. Follath


The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharmacokinetic parameters. Following the rapid initial distribution, biphasic elimination with half lives of 1.99 h (t1/2β) and 36.89 h (t1/2γ) was demonstrated. Measurable amounts of NM were excreted in the urine for up to 72 h. The volume of distribution at steady-state (Vdss) of 0.68 l/kg was 3 to 4 times larger than previously reported for this antibiotic. NM plasma clearance was 91 ml/min and the renal clearance was 67 ml/min. The data indicate that on repetitive dosing the amount of drug in the body would be considerably underestimated if the prolonged terminal elimination phase were not taken into account. During prolonged treatment, accumulation of NM in renal and other tissues is likely to occur, as has been described for other aminoglycosides. The possible consequences of this pharmacokinetic behaviour are discussed.

Key words

netilmicin radioenzymatic assay drug accumulation pharmacokinetics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kabins, S. A., Nathan, C., Cohen, S.: In vitro comparison of netilmicin, a semisynthetic derivative of sisomicin, and four other aminoglycoside antibiotics. Antimicrob. Agents Chemother.10, 139–145 (1976)Google Scholar
  2. 2.
    Rahal, J. J., Siberkoff, M. S., Kagan, K., Moldover, N. H.: Bactericidal efficacy of Sch 20569 and amikacin against gentamicin-sensitive and — resistant organisms. Antimicrob. Agents Chemother.9, 595–599 (1976)Google Scholar
  3. 3.
    Jahre, J. A., Fu, K. P., Neu, H. C.: Kinetics of netilmicin and gentamicin. Clin. Pharmacol. Ther.23, 591–597 (1978)Google Scholar
  4. 4.
    Pechere, J. C., Dugal, R., Pechere, M. M.: Kinetics of netilmicin in man. Clin. Pharmacol. Ther.23, 677–684 (1978)Google Scholar
  5. 5.
    Haas, M. J., Davies, J.: Enzymatic acetilation as a means of determining serum aminoglycoside concentrations. Antimicrob. Agents Chemother.4, 497–499 (1973)Google Scholar
  6. 6.
    Broughall, J. M., Reeves, D. S.: The actyltransferase enzyme method for the assay of serum gentamicin concentrations and a comparison with other methods. J. Clin. Pathol.28, 140–145 (1975)Google Scholar
  7. 7.
    Metzler, C. M.: A user's manual for Nonlin. Upjohn Co., Technical Report 7292/69/7292/005, Kalamazoo, MI (1969)Google Scholar
  8. 8.
    Gibaldi, M., Perrier, D.: Pharmacokinetics. pp. 89–96. New York: Marcel Dekker 1975Google Scholar
  9. 9.
    Lode, H., Kemmerich, B., Koeppe, P.: Comparative clinical pharmacology of gentamicin, sisomicin, and tobramycin. Antimicrob. Agents Chemother.8, 396–401 (1975)Google Scholar
  10. 10.
    Regamey, C., Gordon, R. C., Kirby, M. M.: Comparative pharmacokinetics of tobramycin and gentamicin. Clin. Pharmacol. Ther.14, 396–403 (1973)Google Scholar
  11. 11.
    Luft, F. C., Bloch, R., Sloan, R. S., Yum, M. N., Costello, R., Maxwell, D.: Comparative nephrotoxicity of aminoglycoside antibiotics in rats. J. Infect. Dis.138, 541–545 (1978)Google Scholar
  12. 12.
    Marre, R., Beck, H., Züllich, B., Husstedt, W., Freiesleben, H.: Animal studies on accumulation of 11 aminoglycosides in renal tissue. In: Current Chemotherapy. Siegenthaler, W., Luethy, R., (eds.), pp. 955–957. Washington DC: American Society for Microbiology 1978Google Scholar
  13. 13.
    Edwards, C. Q., Smith, C. R., Baughman, K. L., Rogers, J. F., Lietman, P. S.: Concentrations of gentamicin and amikacin in human kidneys. Antimicrob. Agents Chemother.9, 925–927, (1976)Google Scholar
  14. 14.
    Luft, F. C., Luft, M. N., Walker, P. D., Kleit, S. A.: Gentamicin gradient patterns and morphological changes in human kidneys. Nephron18, 167–174 (1977)Google Scholar
  15. 15.
    Schentag, J. J., Jusko, W. J., Vance, J. W., Cumbo, T. J., Abrutyn, E., Delattre, M., Gerbracht, L. M.: Gentamicin disposition and tissue accumulation on multiple dosing. J. Pharmacokinet. Biopharm.5, 559–577 (1977)Google Scholar
  16. 16.
    Schentag, J. J., Lasezkay, G., Cumbo, T. J., Plaut, M. E., Jusko, W. J.: Accumulation pharmacokinetics of tobramycin Antimicrob. Agents Chemother.13, 649–656 (1978)Google Scholar
  17. 17.
    Kahlmeter, G., Jonsson, S., Kamme, C.: Multiple-compartment pharmacokinetics of tobramycin. In: Current Chemotherapy. Siegenthaler, W., Luethy, R., (eds.), pp. 912–915, Washington D.C.: American Society for Microbiology 1978Google Scholar
  18. 18.
    Follath, F., Spring, P., Wenk, M., Benet, L. Z., Dettli, L.: Comparative pharmacokinetics of sisomicin and netilmicin in healthy volunteers. In: Current Chemotherapy. Siegenthaler W., Luethy, R., (eds.), II, pp. 979–980. Washington D.C.: American Society for Microbiology 1978Google Scholar
  19. 19.
    Vozeh, S., Wenk, M., Spring, P., Follath, F.: Verzögerte Ausscheidung der Aminoglykosid-Antibiotika. Bedeutung für die klinische Anwendung. Schweiz. Med. Wochenschr. (in press 1979)Google Scholar
  20. 20.
    Mawer, G. E., Ahmad, R., Dobbs, S. M. et al: Prescribing aids for gentamicin. Br. J. Clin. Pharmacol.1, 45–50 (1974)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • M. Wenk
    • 1
  • P. Spring
    • 1
  • S. Vozeh
    • 1
  • F. Follath
    • 1
  1. 1.Division of Clinical Pharmacology, Department of MedicineKantonsspitalBaselSwitzerland

Personalised recommendations