Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations. (April 2017)

• Record Type: Journal Article
• Authors: Cooney, Lewis; McBride, Antonia; Lilley, Andrew; Sinha, Ian; Johnson, Trevor N.; Hawcutt, Daniel B.
• Is Part Of: Pulmonary pharmacology & therapeutics. Volume 43(2017:Apr.)
• Page Start: 6
• Page End: 11
• Publication Date: 2017-04
• Subjects: Pharmacokinetics -- Aminophylline -- Paediatric -- PBPK modelling -- Dosing; Respiratory organs -- Diseases -- Chemotherapy -- Periodicals; 615.7205
• DOI: 10.1016/j.pupt.2017.01.007
• Languages: English
• ISSNs: 1094-5539

Abstract

Abstract: Objective: To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline. Methods: Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software. Results: 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 Cmax 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. Conclusion: 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).