Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions†

  1. Irene Krämer PhD1,*,
  2. Astrid Schwabe PhD1,
  3. Ralf Lichtinghagen PhD3,
  4. Wolfgang Kamin MD2

Article first published online: 5 DEC 2008

DOI: 10.1002/ppul.20955

Issue

Pediatric Pulmonology

Pediatric Pulmonology

Volume 44, Issue 2, pages 134–141, February 2009

Additional Information

How to Cite

Krämer, I., Schwabe, A., Lichtinghagen, R. and Kamin, W. (2009), Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions. Pediatric Pulmonology, 44: 134–141. doi: 10.1002/ppul.20955

Author Information

  1. 1

    Department of Pharmacy, Johannes Gutenberg-Universität, Mainz, Germany

  2. 2

    Childrens Hospital, Johannes Gutenberg-Universität, Mainz, Germany

  3. 3

    Department of Clinical Chemistry, Medizinische Hochschule Hannover, Hannover, Germany

*Department of Pharmacy, Johannes Gutenberg-Universität, Langenbeckstraße 1, D-55101 Mainz, Germany.

  1. †

    Pulmozyme®, Tobi®, and Gernebcin® were kindly provided by Roche, Chiron, and Infectopharm, but the companies had absolutely no role in the conduct of the experiments. There is no conflict of interest for the authors with the facts presented.

Publication History

  1. Issue published online: 20 JAN 2009
  2. Article first published online: 5 DEC 2008
  3. Manuscript Revised: 23 JUL 2008
  4. Manuscript Accepted: 23 JUL 2008
  5. Manuscript Received: 21 OCT 2007

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (121K)

Keywords:

  • cystic fibrosis;
  • multiple drug inhalation solution;
  • compatibility;
  • sodium metabisulfite;
  • dornase alfa;
  • tobramycin

Abstract

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of the nebulizer solution dornase alfa (Pulmozyme®) with tobramycin nebulizer solutions (TOBI® and GERNEBCIN® 80 mg) are physico-chemically compatible. Drug combinations were prepared by mixing the content of one respule Pulmozyme® with either one respule TOBI® or one ampoule GERNEBCIN® 80 mg. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity and tobramycin concentrations were determined by using a kinetic colorimetric DNase activity assay and a fluorescence immunoassay, respectively. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Tobramycin concentration was not affected by mixing the drug products. In spite of the high variability of the dornase alfa potency assay, it is obvious that activity is especially affected by sodium metabisulfite, used as excipient in GERNEBCIN®. Patients should be advised, not to mix Pulmozyme® with GERNEBCIN® because of the incompatibility reaction. Further analytical studies are needed in order to determine the integrity and activity of dornase alfa in mixtures of Pulmozyme® with TOBI®. Finally clinical studies are necessary in order to demonstrate equivalent efficacy and safety of simultaneous inhalation in comparison to consecutive inhalation of both drugs. Pediatr Pulmonol. 2009; 44:134–141. © 2008 Wiley-Liss, Inc.

Get PDF (121K)