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. 1991 Nov;35(11):2401–2406. doi: 10.1128/aac.35.11.2401

Effect of isepamicin dosing scheme on concentration in cochlear tissue.

P J Govaerts 1, J Claes 1, P H Van de Heyning 1, M P Derde 1, L Kaufman 1, J F Marquet 1, M E De Broe 1
PMCID: PMC245392  PMID: 1804014

Abstract

To investigate the possible effect of the dosing scheme of aminoglycosides on their concentration in the cochlear tissue, we gave two groups of 12 guinea pigs subcutaneous doses of 45 mg of isepamicin (ca. 30 mg of active product) per kg of body weight daily for eight consecutive days. The first group received the drug by continuous infusion, while the second group received it by single daily injection. On the final day of administration, the animals were sacrificed and the cochlear tissue was removed. The tissues from the cochleas of pairs of guinea pigs were pooled. The isepamicin concentrations in the cochlear duct tissue (organ of Corti plus lateral wall) and the cochlear nerve tissue were determined separately. Hearing levels before and after treatment were assessed by means of frequency-specific auditory brain stem responses (ABR). The creatinine level in serum was determined on the last day of the administration. None of the animals in either group showed signs of renal insufficiency or of hearing impairment. The median isepamicin concentration in the cochlear duct was 2.40 micrograms/mg of protein after continuous administration and 2.50 micrograms/mg of protein after once-daily administration, compared with the concentration in the cochlear nerve, where it was 1.93 micrograms/mg of protein after continuous administration and 2.59 micrograms/mg of protein after once-daily administration. These differences are statistically insignificant. The results give evidence for linear uptake kinetics of isepamicin in the inner ear tissue and may be directly relevant to the clinical dosing of the drug.

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Selected References

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

  1. Bamonte F., Dionisotti S., Gamba M., Ongini E., Arpini A., Melone G. Relation of dosing regimen to aminoglycoside ototoxicity: evaluation of auditory damage in the guinea pig. Chemotherapy. 1990;36(1):41–50. doi: 10.1159/000238747. [DOI] [PubMed] [Google Scholar]
  2. Beaubien A. R., Desjardins S., Ormsby E., Bayne A., Carrier K., Cauchy M. J., Henri R., Hodgen M., Salley J., St Pierre A. Incidence of amikacin ototoxicity: a sigmoid function of total drug exposure independent of plasma levels. Am J Otolaryngol. 1989 Jul-Aug;10(4):234–243. doi: 10.1016/0196-0709(89)90002-1. [DOI] [PubMed] [Google Scholar]
  3. Bock G. R., Steel K. P. Use of albino animals for auditory research. Hear Res. 1984 Feb;13(2):201–202. doi: 10.1016/0378-5955(84)90109-6. [DOI] [PubMed] [Google Scholar]
  4. Conlee J. W., Gill S. S., McCandless P. T., Creel D. J. Differential susceptibility to gentamicin ototoxicity between albino and pigmented guinea pigs. Hear Res. 1989 Aug;41(1):43–51. doi: 10.1016/0378-5955(89)90177-9. [DOI] [PubMed] [Google Scholar]
  5. Creel D. Inappropriate use of albino animals as models in research. Pharmacol Biochem Behav. 1980 Jun;12(6):969–967. doi: 10.1016/0091-3057(80)90461-x. [DOI] [PubMed] [Google Scholar]
  6. De Broe M. E., Giuliano R. A., Verpooten G. A. Choice of drug and dosage regimen. Two important risk factors for aminoglycoside nephrotoxicity. Am J Med. 1986 Jun 30;80(6B):115–118. doi: 10.1016/0002-9343(86)90488-2. [DOI] [PubMed] [Google Scholar]
  7. Desrochers C. S., Schacht J. Assay of aminoglycosides is influenced by tissue homogenization technique. Experientia. 1981 Dec 15;37(12):1357–1358. doi: 10.1007/BF01948411. [DOI] [PubMed] [Google Scholar]
  8. Desrochers C. S., Schacht J. Neomycin concentrations in inner ear tissues and other organs of the guinea pig after chronic drug administration. Acta Otolaryngol. 1982;93(1-6):233–236. doi: 10.3109/00016488209130877. [DOI] [PubMed] [Google Scholar]
  9. Dreschler W. A., van der Hulst R. J., Tange R. A., Urbanus N. A. Role of high-frequency audiometry in the early detection of ototoxicity. II. Clinical Aspects. Audiology. 1989;28(4):211–220. doi: 10.3109/00206098909081626. [DOI] [PubMed] [Google Scholar]
  10. Giuliano R. A., Verpooten G. A., De Broe M. E. The effect of dosing strategy on kidney cortical accumulation of aminoglycosides in rats. Am J Kidney Dis. 1986 Nov;8(5):297–303. doi: 10.1016/s0272-6386(86)80101-9. [DOI] [PubMed] [Google Scholar]
  11. Giuliano R. A., Verpooten G. A., Pollet D. E., Verbist L., Scharpé S. L., De Broe M. E. Improved procedure for extracting aminoglycosides from renal cortical tissue. Antimicrob Agents Chemother. 1984 Jun;25(6):783–784. doi: 10.1128/aac.25.6.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Giuliano R. A., Verpooten G. A., Verbist L., Wedeen R. P., De Broe M. E. In vivo uptake kinetics of aminoglycosides in the kidney cortex of rats. J Pharmacol Exp Ther. 1986 Feb;236(2):470–475. [PubMed] [Google Scholar]
  13. Govaerts P. J., Claes J., van de Heyning P. H., Jorens P. G., Marquet J., De Broe M. E. Aminoglycoside-induced ototoxicity. Toxicol Lett. 1990 Aug;52(3):227–251. doi: 10.1016/0378-4274(90)90033-i. [DOI] [PubMed] [Google Scholar]
  14. Koitchev K., Guilhaume A., Cazals Y., Aran J. M. Spiral ganglion changes after massive aminoglycoside treatment in the guinea pig. Counts and ultrastructure. Acta Otolaryngol. 1982 Nov-Dec;94(5-6):431–438. doi: 10.3109/00016488209128931. [DOI] [PubMed] [Google Scholar]
  15. Maller R., Isaksson B., Nilsson L., Sörén L. A study of amikacin given once versus twice daily in serious infections. J Antimicrob Chemother. 1988 Jul;22(1):75–79. doi: 10.1093/jac/22.1.75. [DOI] [PubMed] [Google Scholar]
  16. Schacht J. Molecular mechanisms of drug-induced hearing loss. Hear Res. 1986;22:297–304. doi: 10.1016/0378-5955(86)90105-x. [DOI] [PubMed] [Google Scholar]
  17. Sera K., Harada Y., Tagashira N., Suzuki M., Hirakawa K., Ohya T. Morphological changes in the vestibular epithelia and ganglion induced by ototoxic drug. Scanning Microsc. 1987 Sep;1(3):1191–1197. [PubMed] [Google Scholar]
  18. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  19. Tran Ba Huy P., Bernard P., Schacht J. Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs. J Clin Invest. 1986 May;77(5):1492–1500. doi: 10.1172/JCI112463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Verpooten G. A., Giuliano R. A., Verbist L., Eestermans G., De Broe M. E. Once-daily dosing decreases renal accumulation of gentamicin and netilmicin. Clin Pharmacol Ther. 1989 Jan;45(1):22–27. doi: 10.1038/clpt.1989.4. [DOI] [PubMed] [Google Scholar]
  21. Wästerström S. A., Bredberg G. Ototoxicity of kanamycin in albino and pigmented guinea pigs. II. A scanning electron microscopic study. Am J Otol. 1986 Jan;7(1):19–24. [PubMed] [Google Scholar]

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