Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations


Cooney, Lewis, McBride, Antonia, Lilley, Andrew, Sinha, Ian, Johnson, Trevor N and Hawcutt, Daniel B ORCID: 0000-0002-8120-6507 (2017) Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations. PULMONARY PHARMACOLOGY & THERAPEUTICS, 43. pp. 6-11.

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Abstract

<h4>Objective</h4>To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline.<h4>Methods</h4>Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software.<h4>Results</h4>Thirty-eight admissions (25 children) were included. Children with aminophylline levels ≥10 mg/l had equivalent clinical outcomes compared to those <10 mg/L, and adverse effects occurred in 57%. Therapeutic drug monitoring (TDM) data correlated well with PBPK model. PBPK modelling of a 5 mg/kg iv loading dose (≤18yr) shows a mean C<sub>max</sub> of 8.99 mg/L (5th-95th centiles 5.5-13.7 mg/L), with 70.3% of subjects <10 mg/L, 29.4% achieving 10-20 mg/L, and 0.1% > 20 mg/L. For an aminophylline infusion (0-12 y) of 1.0  mg/kg/h, the mean steady state infusion concentration was 16.4 mg/L, (5th-95th centiles 5.3-32 mg/L), with 26.8% having a serum concentration >20 mg/L. For 12-18yr receiving 0.5  mg/kg/h infusion, the mean steady state infusion concentration was 9.37 mg/L (5th-95th centiles 3.4-18 mg/L), with 59.8% having a serum concentration <10 mg/L.<h4>Conclusion</h4>PBPK software modelling correlates well with clinical data. Current aminophylline iv loading dosage recommendations achieve levels <10 mg/l in 70% of children. Routine TDM may need altering as low risk of toxicity (>20 mg/l).

Item Type: Article
Uncontrolled Keywords: Pharmacokinetics, Aminophylline, Paediatric, PBPK modelling, Dosing
Depositing User: Symplectic Admin
Date Deposited: 18 Jan 2017 08:27
Last Modified: 19 Jan 2023 07:20
DOI: 10.1016/j.pupt.2017.01.007
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3005283
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