Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 Jan;41(1):184–187. doi: 10.1128/aac.41.1.184

Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis.

D J Touw 1, F A Jacobs 1, R W Brimicombe 1, H G Heijerman 1, W Bakker 1, D D Briemer 1
PMCID: PMC163682  PMID: 8980777

Abstract

This study was performed to determine the clinical pharmacokinetics of tobramycin in six patients with cystic fibrosis (CF) after inhalation of 600 mg. Tobramycin was administered with an ultrasonic nebulizer (WISTO SENIOR). Blood and urine were sampled until 24 h after inhalation. Maximum tobramycin levels in serum varied from 0.19 to 2.57 mg/liter (mean 1.27 mg/liter; standard deviation, 1.07 mg/liter). Systemic availability (calculated from urinary output) ranged from 6.0 to 27.4% (mean, 17.5%; standard deviation, 8.8%). The results illustrate that, provided that the systemic availability of tobramycin is a reflection of pulmonary deposition, inhalation studies with CF patients should have a concentration-controlled design. Furthermore, reliance on dose recommendations from the literature for a new patient starting on this treatment is not justified, but it is mandatory that deposition kinetics be studied for each patient and for each nebulizer. It may well be that, with higher levels of deposition, dosages lower than those recommended in the literature will suffice to obtain the desired clinical effect. In addition, the reverse may also be the case.

Full Text

The Full Text of this article is available as a PDF (156.5 KB).

Selected References

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

  1. Bentur Y., Hummel D., Roifman C. M., Giesbrecht E., Koren G. Interpretation of excessive levels of inhaled tobramycin. Ther Drug Monit. 1989;11(1):109–110. doi: 10.1097/00007691-198901000-00022. [DOI] [PubMed] [Google Scholar]
  2. Contrepois A., Brion N., Garaud J. J., Faurisson F., Delatour F., Levy J. C., Deybach J. C., Carbon C. Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans. Antimicrob Agents Chemother. 1985 Apr;27(4):520–524. doi: 10.1128/aac.27.4.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Crosby S. S., Edwards W. A., Brennan C., Dellinger E. P., Bauer L. A. Systemic absorption of endotracheally administered aminoglycosides in seriously ill patients with pneumonia. Antimicrob Agents Chemother. 1987 Jun;31(6):850–853. doi: 10.1128/aac.31.6.850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ilowite J. S., Gorvoy J. D., Smaldone G. C. Quantitative deposition of aerosolized gentamicin in cystic fibrosis. Am Rev Respir Dis. 1987 Dec;136(6):1445–1449. doi: 10.1164/ajrccm/136.6.1445. [DOI] [PubMed] [Google Scholar]
  5. Jensen T., Pedersen S. S., Garne S., Heilmann C., Høiby N., Koch C. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. J Antimicrob Chemother. 1987 Jun;19(6):831–838. doi: 10.1093/jac/19.6.831. [DOI] [PubMed] [Google Scholar]
  6. Kun P., Landau L. I., Phelan P. D. Nebulized gentamicin in children and adolescents with cystic fibrosis. Aust Paediatr J. 1984 Mar;20(1):43–45. doi: 10.1111/j.1440-1754.1984.tb00035.x. [DOI] [PubMed] [Google Scholar]
  7. MacLusky I. B., Gold R., Corey M., Levison H. Long-term effects of inhaled tobramycin in patients with cystic fibrosis colonized with Pseudomonas aeruginosa. Pediatr Pulmonol. 1989;7(1):42–48. doi: 10.1002/ppul.1950070110. [DOI] [PubMed] [Google Scholar]
  8. Mukhopadhyay S., Baer S., Blanshard J., Coleman M., Carswell F. Assessment of potential ototoxicity following high-dose nebulized tobramycin in patients with cystic fibrosis. J Antimicrob Chemother. 1993 Mar;31(3):429–436. doi: 10.1093/jac/31.3.429. [DOI] [PubMed] [Google Scholar]
  9. Mukhopadhyay S., Staddon G. E., Eastman C., Palmer M., Davies E. R., Carswell F. The quantitative distribution of nebulized antibiotic in the lung in cystic fibrosis. Respir Med. 1994 Mar;88(3):203–211. doi: 10.1016/s0954-6111(05)80348-8. [DOI] [PubMed] [Google Scholar]
  10. Nolan G., Moivor P., Levison H., Fleming P. C., Corey M., Gold R. Antibiotic prophylaxis in cystic fibrosis: inhaled cephaloridine as an adjunct to oral cloxacillin. J Pediatr. 1982 Oct;101(4):626–630. doi: 10.1016/s0022-3476(82)80726-9. [DOI] [PubMed] [Google Scholar]
  11. Ramsey B. W., Dorkin H. L., Eisenberg J. D., Gibson R. L., Harwood I. R., Kravitz R. M., Schidlow D. V., Wilmott R. W., Astley S. J., McBurnie M. A. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993 Jun 17;328(24):1740–1746. doi: 10.1056/NEJM199306173282403. [DOI] [PubMed] [Google Scholar]
  12. Rodman D. P., Maxwell A. J., McKnight J. T. Extended dosage intervals for aminoglycosides. Am J Hosp Pharm. 1994 Aug 15;51(16):2016–2021. [PubMed] [Google Scholar]
  13. Smith A. L., Ramsey B. W., Hedges D. L., Hack B., Williams-Warren J., Weber A., Gore E. J., Redding G. J. Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis. Pediatr Pulmonol. 1989;7(4):265–271. doi: 10.1002/ppul.1950070413. [DOI] [PubMed] [Google Scholar]
  14. Stead R. J., Hodson M. E., Batten J. C. Inhaled ceftazidime compared with gentamicin and carbenicillin in older patients with cystic fibrosis infected with Pseudomonas aeruginosa. Br J Dis Chest. 1987 Jul;81(3):272–279. doi: 10.1016/0007-0971(87)90161-6. [DOI] [PubMed] [Google Scholar]
  15. Steinkamp G., Tümmler B., Gappa M., Albus A., Potel J., Döring G., von der Hardt H. Long-term tobramycin aerosol therapy in cystic fibrosis. Pediatr Pulmonol. 1989;6(2):91–98. doi: 10.1002/ppul.1950060207. [DOI] [PubMed] [Google Scholar]
  16. Touw D. J., Brimicombe R. W., Hodson M. E., Heijerman H. G., Bakker W. Inhalation of antibiotics in cystic fibrosis. Eur Respir J. 1995 Sep;8(9):1594–1604. [PubMed] [Google Scholar]
  17. Touw D. J., Vinks A. A., Heijerman H. G., Bakker W. Validation of tobramycin monitoring in adolescent and adult patients with cystic fibrosis. Ther Drug Monit. 1993 Feb;15(1):52–59. doi: 10.1097/00007691-199302000-00010. [DOI] [PubMed] [Google Scholar]
  18. Touw D. J., de Graaf A. I., de Goede P. Evaluation of a fluorescence polarographic immunoassay with increased sensitivity for measurement of low concentrations of tobramycin in serum. Ther Drug Monit. 1996 Apr;18(2):189–193. doi: 10.1097/00007691-199604000-00013. [DOI] [PubMed] [Google Scholar]
  19. Town D. J., Vinks A. A., Jacobs F., Heijerman H. G., Bakker W. Creatinine clearance as predictor of tobramycin elimination in adult patients with cystic fibrosis. Ther Drug Monit. 1996 Oct;18(5):562–569. doi: 10.1097/00007691-199610000-00007. [DOI] [PubMed] [Google Scholar]

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

RESOURCES