Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Nov;35(11):2382–2387. doi: 10.1128/aac.35.11.2382

Isepamicin disposition in subjects with various degrees of renal function.

C E Halstenson 1, J S Kelloway 1, M B Affrime 1, C C Lin 1, M A Teal 1, B E Shapiro 1, W M Awni 1
PMCID: PMC245389  PMID: 1804011

Abstract

The disposition of isepamicin, an investigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function. The subjects were divided into five groups: those with normal renal function (creatinine clearance [CLCR], greater than 80 ml/min/1.73 m2), those with mild renal insufficiency (CLCR, 50 to 80 ml/min/1.73 m2), those with moderate renal insufficiency (CLCR, 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CLCR, 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CLCR, less than 5 ml/min/1.73 m2). Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period. The volumes of distribution of isepamicin were not significantly different among the five groups of patients. The total body clearance (CLP) and renal clearance (CLR) of isepamicin significantly decreased as CLCR decreased. The CLP of isepamicin and CLCR were significantly related [(COP = 0.391.[CLCR] + 1.83; r2 = 0.878)]. Nonrenal clearance of isepamicin did not differ between groups. Hemodialysis augmented the CLP of isepamicin by approximately 25-fold. The amount of isepamicin recovered in the dialysate was 60.6 +/- 15.8% of the dose administered. The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 +/- 0.7 h. Concentrations in plasma increased 32.7 +/- 22.9% over that measured at the end of hemodialysis. These data indicate that dosage adjustments are necessary in subjects with decreased renal function.

Full text

PDF
2382

Selected References

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

  1. Bauer L. A. Rebound gentamicin levels after hemodialysis. Ther Drug Monit. 1982;4(1):99–101. doi: 10.1097/00007691-198204000-00015. [DOI] [PubMed] [Google Scholar]
  2. Bechtol L. D., Black H. R. Tobramycin in renal impairment. Am J Med Sci. 1975 May-Jun;269(3):317–321. doi: 10.1097/00000441-197505000-00004. [DOI] [PubMed] [Google Scholar]
  3. Gyselynck A. M., Forrey A., Cutler R. Pharmacokinetics of gentamicin: distribution and plasma and renal clearance. J Infect Dis. 1971 Dec;124 (Suppl):S70–S76. doi: 10.1093/infdis/124.supplement_1.s70. [DOI] [PubMed] [Google Scholar]
  4. Halstenson C. E., Berkseth R. O., Mann H. J., Matzke G. R. Aminoglycoside redistribution phenomenon after hemodialysis: netilmicin and tobramycin. Int J Clin Pharmacol Ther Toxicol. 1987 Jan;25(1):50–55. [PubMed] [Google Scholar]
  5. 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]
  6. Maloney J. A., Awni W. M. High-performance liquid chromatographic determination of isepamicin in plasma, urine and dialysate. J Chromatogr. 1990 Apr 6;526(2):487–496. doi: 10.1016/s0378-4347(00)82530-x. [DOI] [PubMed] [Google Scholar]
  7. Matzke G. R., Halstenson C. E., Keane W. F. Hemodialysis elimination rates and clearance of gentamicin and tobramycin. Antimicrob Agents Chemother. 1984 Jan;25(1):128–130. doi: 10.1128/aac.25.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Matzke G. R., Millikin S. P., Kovarik J. M. Variability in pharmacokinetic values for gentamicin, tobramycin, and netilmicin in patients with renal insufficiency. Clin Pharm. 1989 Nov;8(11):800–806. [PubMed] [Google Scholar]
  9. Moore R. D., Smith C. R., Lietman P. S. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. Am J Med. 1984 Oct;77(4):657–662. doi: 10.1016/0002-9343(84)90358-9. [DOI] [PubMed] [Google Scholar]
  10. Moore R. D., Smith C. R., Lietman P. S. The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis. 1984 Mar;149(3):443–448. doi: 10.1093/infdis/149.3.443. [DOI] [PubMed] [Google Scholar]
  11. Murphy J. E. Aminoglycosides: another look at current and future roles in antimicrobial therapy. Pharmacotherapy. 1990;10(3):217–223. [PubMed] [Google Scholar]
  12. Nagabhushan T. L., Cooper A. B., Tsai H., Daniels P. J., Miller G. H. The syntheses and biological properties of 1-N-(S-4-amino-2-hydroxybutyryl)-gentamicin B and 1-N-(S-3-amino-2-hydroxypropionyl)-gentamicin B. J Antibiot (Tokyo) 1978 Jul;31(7):681–687. doi: 10.7164/antibiotics.31.681. [DOI] [PubMed] [Google Scholar]
  13. Noone P., Parsons T. M., Pattison J. R., Slack R. C., Garfield-Davies D., Hughes K. Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. Br Med J. 1974 Mar 16;1(5906):477–481. doi: 10.1136/bmj.1.5906.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pechère J. C., Pechère M. M., Dugal R. Clinical pharmacokinetics of sisomicin: dosage schedules in renal-impaired patients. Antimicrob Agents Chemother. 1976 May;9(5):761–765. doi: 10.1128/aac.9.5.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Plantier J., Forrey A. W., O'Neill M. A., Blair A. D., Christopher T. G., Cutler R. E. Pharmacokinetics of amikacin in patients with normal or impaired renal function: radioenzymatic acetylation assay. J Infect Dis. 1976 Nov;134(Suppl):S323–S330. doi: 10.1093/infdis/135.supplement_2.s323. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. 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]
  19. Takumida M., Nishida I., Nikaido M., Hirakawa K., Harada Y., Bagger-Sjöbäck D. Effect of dosing schedule on aminoglycoside ototoxicity: comparative cochlear ototoxicity of amikacin and isepamicin. ORL J Otorhinolaryngol Relat Spec. 1990;52(6):341–349. doi: 10.1159/000276162. [DOI] [PubMed] [Google Scholar]
  20. Welling P. G., Baumueller A., Lau C. C., Madsen P. O. Netilmicin pharmacokinetics after single intravenous doses to elderly male patients. Antimicrob Agents Chemother. 1977 Sep;12(3):328–334. doi: 10.1128/aac.12.3.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yamaoka K., Nakagawa T., Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 1978 Apr;6(2):165–175. doi: 10.1007/BF01117450. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES