Aminophylline: Developing Evidence Based Dosage and Monitoring Strategies for Children



Cooney, L
(2016) Aminophylline: Developing Evidence Based Dosage and Monitoring Strategies for Children. Master of Philosophy thesis, University of Liverpool.

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Abstract

Background: Intravenous aminophylline is used to treat childhood asthma exacerbations. Children who receive aminophylline have serum drug levels measured, due to its purported narrow therapeutic range and variable clearance rates. The results of therapeutic drug monitoring are used to inform subsequent clinical decisions such as dosage. It is not known whether these practices maximise the safety and efficacy profile of aminophylline, and the mechanisms underlying the interindividual variation in clearance rates are poorly understood. Aims: To assess the evidence base of current aminophylline prescribing practices, and to investigate the mechanisms underlying the variability aminophylline clearance rates. Methods: Two systematic reviews were undertaken to investigate aminophylline prescribing practices. The first review compared outcomes of children who achieved serum theophylline concentrations between 10-20mg/l with those who did not, and the second review compared different dosage regimens of intravenous aminophylline. An audit of adherence to aminophylline prescribing practices was performed, with subsequent pharmacokinetic analysis. Finally, a pilot cohort study was used to investigate the role of genetics in the variability of aminophylline clearance. Results: The systematic reviews found a poor correlation between serum drug levels, dosage and clinical outcomes in children receiving intravenous aminophylline. Good adherence to prescribing practices was found in our audit, however the effectiveness of treatment for acute asthma is no worse if the therapeutic range is not achieved in the first 12 hours of treatment. The cohort study has not yet recruited sufficient participants to assess the effect of genes on aminophylline clearance. Conclusion: Current dosage and monitoring practices of intravenous aminophylline in childhood asthma exacerbations have a poor evidence base. Measuring aminophylline following administration may be unnecessary, due to the poor relationship between serum drug levels and clinical outcomes, and current dosing strategies may not maximise the benefit of the drug. Most children who receive loading doses do not achieve therapeutic levels, and the mechanisms underlying this variability remain poorly understood.

Item Type: Thesis (Master of Philosophy)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 14 Dec 2016 08:36
Last Modified: 19 Jan 2023 07:30
DOI: 10.17638/03003369
Supervisors:
  • Hawcutt, D
  • Sinha, I
URI: https://livrepository.liverpool.ac.uk/id/eprint/3003369