PMID- 28108402
OWN - NLM
STAT- MEDLINE
DCOM- 20171108
LR  - 20180921
IS  - 1522-9629 (Electronic)
IS  - 1094-5539 (Linking)
VI  - 43
DP  - 2017 Apr
TI  - Using pharmacokinetic modelling to improve prescribing practices of intravenous 
      aminophylline in childhood asthma exacerbations.
PG  - 6-11
LID - S1094-5539(16)30128-6 [pii]
LID - 10.1016/j.pupt.2017.01.007 [doi]
AB  - 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 
      C(max) 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).
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Cooney, Lewis
AU  - Cooney L
AD  - Medical School, University of Liverpool, UK.
FAU - McBride, Antonia
AU  - McBride A
AD  - Alder Hey Children's Hospital, Liverpool, UK.
FAU - Lilley, Andrew
AU  - Lilley A
AD  - Alder Hey Children's Hospital, Liverpool, UK.
FAU - Sinha, Ian
AU  - Sinha I
AD  - Alder Hey Children's Hospital, Liverpool, UK.
FAU - Johnson, Trevor N
AU  - Johnson TN
AD  - Simcyp, Sheffield, UK.
FAU - Hawcutt, Daniel B
AU  - Hawcutt DB
AD  - Alder Hey Children's Hospital, Liverpool, UK; Department of Women's and 
      Children's Health, University of Liverpool, UK; NIHR Alder Hey Clinical Research 
      Facility, Alder Hey Children's Hospital, Liverpool, UK. Electronic address: 
      D.hawcutt@liv.ac.uk.
LA  - eng
GR  - Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170118
PL  - England
TA  - Pulm Pharmacol Ther
JT  - Pulmonary pharmacology & therapeutics
JID - 9715279
RN  - 0 (Bronchodilator Agents)
RN  - 27Y3KJK423 (Aminophylline)
SB  - IM
MH  - Administration, Intravenous
MH  - Adolescent
MH  - Aminophylline/administration & dosage/*pharmacokinetics
MH  - Asthma/*drug therapy
MH  - Bronchodilator Agents/administration & dosage/*pharmacokinetics
MH  - Child
MH  - Child, Preschool
MH  - Computer Simulation
MH  - Dose-Response Relationship, Drug
MH  - Drug Monitoring/methods
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - *Models, Biological
MH  - Prospective Studies
OTO - NOTNLM
OT  - Aminophylline
OT  - Dosing
OT  - PBPK modelling
OT  - Paediatric
OT  - Pharmacokinetics
EDAT- 2017/01/22 06:00
MHDA- 2017/11/09 06:00
CRDT- 2017/01/22 06:00
PHST- 2016/10/12 00:00 [received]
PHST- 2017/01/14 00:00 [accepted]
PHST- 2017/01/22 06:00 [pubmed]
PHST- 2017/11/09 06:00 [medline]
PHST- 2017/01/22 06:00 [entrez]
AID - S1094-5539(16)30128-6 [pii]
AID - 10.1016/j.pupt.2017.01.007 [doi]
PST - ppublish
SO  - Pulm Pharmacol Ther. 2017 Apr;43:6-11. doi: 10.1016/j.pupt.2017.01.007. Epub 2017 
      Jan 18.