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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1993 Oct;36(4):372–375. doi: 10.1111/j.1365-2125.1993.tb00380.x

An in vivo assessment of the tobramycin/ticarcillin interaction in cystic fibrosis patients.

G W Roberts 1, R L Nation 1, A O Jarvinen 1, A J Martin 1
PMCID: PMC1364694  PMID: 12959319

Abstract

A non-blinded, randomized, cross-over investigation of the pharmacokinetic interaction between tobramycin and ticarcillin was performed in 18 healthy cystic fibrosis (CF) patients with normal renal function. On consecutive mornings the patients were given either tobramycin intravenously (i.v.) over 3-5 min (TOB phase), or tobramycin i.v. over 3-5 min followed immediately by ticarcillin infused i.v. over 20-30 min (TOB+TIC phase). Capillary blood samples were taken 30 min and 330 min after administration of the tobramycin dose in each phase. Tobramycin was measured in serum by fluorescence polarization immunoassay (TDx). There were decreases in serum tobramycin concentrations of 11% at 30 min (P < 0.001) and 330 min (P = 0.012) when measured in the presence of ticarcillin. No difference in elimination half-life was found (TOB phase 95 +/- 13 min, TOB+TIC phase 95 +/- 13 min, P = 0.86). The volume of distribution and clearance of tobramycin increased by 14% (P < 0.001) and 13% (P < 0.001), respectively, in the presence of ticarcillin. This interaction appears to be of minor clinical importance but pharmacokinetic studies of tobramycin should exclude concurrent use of ticarcillin.

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Selected References

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  1. Anders R. J., Lau A., Sharifi R., Lee M. Comparison of EMIT versus bioassay to evaluate inactivation of tobramycin by piperacillin. Ther Drug Monit. 1987 Dec;9(4):472–477. doi: 10.1097/00007691-198712000-00019. [DOI] [PubMed] [Google Scholar]
  2. Benveniste R., Davies J. Structure-activity relationships among the aminoglycoside antibiotics: role of hydroxyl and amino groups. Antimicrob Agents Chemother. 1973 Oct;4(4):402–409. doi: 10.1128/aac.4.4.402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chow M. S., Quintiliani R., Nightingale C. H. In vivo inactivation of tobramycin by ticarcillin. A case report. JAMA. 1982 Feb 5;247(5):658–659. [PubMed] [Google Scholar]
  4. Ebert S. C., Jorgensen J. H., Drutz D. J., Clementi W. A. Comparative assessment of in vitro inactivation of gentamicin in the presence of carbenicillin by three different gentamicin assay methods. J Clin Microbiol. 1984 Oct;20(4):701–705. doi: 10.1128/jcm.20.4.701-705.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ervin F. R., Bullock W. E., Jr, Nuttall C. E. Inactivation of gentamicin by penicillins in patients with renal failure. Antimicrob Agents Chemother. 1976 Jun;9(6):1004–1011. doi: 10.1128/aac.9.6.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glew R. H., Pavuk R. A. Stability of gentamicin, tobramycin, and amikacin in combination with four beta-lactam antibiotics. Antimicrob Agents Chemother. 1983 Oct;24(4):474–477. doi: 10.1128/aac.24.4.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hale D. C., Jenkins R., Matsen J. M. In-vitro inactivation of aminoglycoside antibiotics by piperacillin and carbenicillin. Am J Clin Pathol. 1980 Sep;74(3):316–319. doi: 10.1093/ajcp/74.3.316. [DOI] [PubMed] [Google Scholar]
  8. Kildoo C. W., Harralson A. F., Folli H. L., Kelly P. C., Nussbaum E. Direct determination of tobramycin clearance in patients with mild-to-moderate cystic fibrosis. Drug Intell Clin Pharm. 1987 Jul-Aug;21(7-8):639–642. doi: 10.1177/1060028087021007-815. [DOI] [PubMed] [Google Scholar]
  9. Konishi H., Goto M., Nakamoto Y., Yamamoto I., Yamashina H. Tobramycin inactivation by carbenicillin, ticarcillin, and piperacillin. Antimicrob Agents Chemother. 1983 May;23(5):653–657. doi: 10.1128/aac.23.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lau A., Lee M., Flascha S., Prasad R., Sharifi R. Effect of piperacillin on tobramycin pharmacokinetics in patients with normal renal function. Antimicrob Agents Chemother. 1983 Oct;24(4):533–537. doi: 10.1128/aac.24.4.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Levy J., Smith A. L., Koup J. R., Williams-Warren J., Ramsey B. Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study. J Pediatr. 1984 Jul;105(1):117–124. doi: 10.1016/s0022-3476(84)80375-3. [DOI] [PubMed] [Google Scholar]
  12. Munzenberger P. J., Commissaris R. L., Massoud N., Hsu M. C. Variability of tobramycin pharmacokinetics in cystic fibrosis. Pediatr Infect Dis J. 1987 Aug;6(8):739–743. doi: 10.1097/00006454-198708000-00009. [DOI] [PubMed] [Google Scholar]
  13. O'Bey K. A., Jim L. K., Gee J. P., Johnson R. M. Temperature dependence of the stability of tobramycin mixed with penicillins in human serum. Am J Hosp Pharm. 1982 Jun;39(6):1005–1008. [PubMed] [Google Scholar]
  14. Pfaller M. A., Granich G. G., Valdes R., Murray P. R. Comparative study of the ability of four aminoglycoside assay techniques to detect the inactivation of aminoglycosides by beta-lactam antibiotics. Diagn Microbiol Infect Dis. 1984 Apr;2(2):93–100. doi: 10.1016/0732-8893(84)90003-8. [DOI] [PubMed] [Google Scholar]
  15. Pickering L. K., Rutherford I. Effect of concentration and time upon inactivation of tobramycin, gentamicin, netilmicin and amikacin by azlocillin, carbenicillin, mecillinam, mezlocillin and piperacillin. J Pharmacol Exp Ther. 1981 May;217(2):345–349. [PubMed] [Google Scholar]
  16. Pieper J. A., Vidal R. A., Schentag J. J. Animal model distinguishing in vitro from in vivo carbenicillin-aminoglycoside interactions. Antimicrob Agents Chemother. 1980 Oct;18(4):604–609. doi: 10.1128/aac.18.4.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pleasants R. A., Williams D. M., Waltner W. E., Knowles M. R. Influence of infusion method on serum tobramycin concentrations in adults with cystic fibrosis. Clin Pharm. 1990 Jul;9(7):541–545. [PubMed] [Google Scholar]
  18. Polk R. E., Kline B. J. Mall order tobramycin serum levels: low values caused by ticarcillin. Am J Hosp Pharm. 1980 Jul;37(7):920–922. [PubMed] [Google Scholar]
  19. Riff L. J., Thomason J. L. Comparative aminoglycoside inactivation by beta-lactam antibiotics. Effects of a cephalosporin and six penicillins on five aminoglycosides. J Antibiot (Tokyo) 1982 Jul;35(7):850–857. doi: 10.7164/antibiotics.35.850. [DOI] [PubMed] [Google Scholar]
  20. Sawchuk R. J., Zaske D. E., Cipolle R. J., Wargin W. A., Strate R. G. Kinetic model for gentamicin dosing with the use of individual patient parameters. Clin Pharmacol Ther. 1977 Mar;21(3):362–369. doi: 10.1002/cpt1977213362. [DOI] [PubMed] [Google Scholar]

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