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Pharmacokinetics of Ibuprofen in Children with Cystic Fibrosis

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Abstract

An exaggerated inflammatory response is responsible for the decline of lung function in patients with cystic fibrosis (CF). Ibuprofen is a potent anti-inflammatory agent that demonstrates inhibition of neutrophil activity in vitro at concentrations between 50 and 100 mg/L, whereas lower concentrations result in an increase in inflammatory mediators. Significant decline in the rate of deterioration of pulmonary function and increased nutritional status were observed in children with CF who were administered long-term high-dosage ibuprofen therapy.

As with many other drugs, CF patients appear to exhibit altered pharmacokinetics of ibuprofen (reduced bioavailability, increased volume of distribution, and more rapid clearance) when compared with healthy controls. However, the absence of studies with intravenous ibuprofen as well as protein binding measurements in patients with CF currently limits the ability to compare the pharmacokinetics with those in other populations. Current studies indicate that there is high interpatient variability in ibuprofen pharmacokinetics among CF patients. Some of this variability can be explained by differences in ibuprofen formulation administered.

Therapeutic drug monitoring of high-dosage ibuprofen therapy is recommended because of the biphasic response to inflammatory mediators demonstrated in vitro as well as the high interpatient variability in pharmacokinetics. Due to the differences in absorption characteristics between ibuprofen formulations, the timing of obtaining blood samples for pharmacokinetic analysis is critical. Maximum a posteriori Bayesian analysis has been shown to provide more accurate and precise estimates of the pharmacokinetic parameters of ibuprofen in children with CF, and may also be a useful tool to further investigate the relationship between measures of drug exposure and efficacy/toxicity outcomes.

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Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Laboratory for Pharmacodynamic Research, School of Pharmacy, University of Southern California, Los Angeles, California, USA

    Emily E. Han,  Paul M. Beringer, Stan G. Louie & Mark A. Gill

  2. Adult Cystic Fibrosis Center, University of Southern California, Los Angeles, California, USA

    Emily E. Han,  Paul M. Beringer & Bertrand J. Shapiro

  3. Keck School of Medicine, University of Southern California, Los Angeles, California, USA

    Paul M. Beringer, Stan G. Louie & Bertrand J. Shapiro

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  1. Emily E. Han
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  2. Paul M. Beringer
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Correspondence to Paul M. Beringer.

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Han, E.E., Beringer, P.M., Louie, S.G. et al. Pharmacokinetics of Ibuprofen in Children with Cystic Fibrosis. Clin Pharmacokinet 43, 145–156 (2004). https://doi.org/10.2165/00003088-200443030-00001

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