Document Detail


Prophylactic ranitidine treatment in critically ill children - a population pharmacokinetic study.
MedLine Citation:
PMID:  23016949     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: to characterise the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. METHODS: Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography and the data were subjected to population pharmacokinetic analysis using nonlinear mixed effects modelling (NONMEM). RESULTS: A one-compartment model best described the plasma concentration profile, with an exponential structure for inter-individual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (-12.618; p<0.001) compared to the weight corrected base model. Final parameter estimates for the population were 32.1 L/hr for total clearance and 285 L for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 hr(-1) and 27.5%, respectively. No significant relationship was found between age and weight corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery shown to significantly reduce clearance by a factor of 0.46. CONCLUSIONS: Currently ranitidine dose recommendations are based on children's weights.
Authors:
Ahmed F Hawwa; Paul M Westwood; Paul S Collier; Jeffrey S Millership; Shirish Yakkundi; Gillian Thurley; Mike D Shields; Anthony J Nunn; Henry L Halliday; James C McElnay
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-28
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  -     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
Affiliation:
Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, United Kingdom.
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