Document Detail


Prophylactic ranitidine treatment in critically ill children--a population pharmacokinetic study.
MedLine Citation:
PMID:  23016949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: To characterize 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.
RESULTS: A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual 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 with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h(-1) 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 h(-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 being shown to reduce clearance significantly by a factor of 0.46.
CONCLUSIONS: Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary.
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; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  75     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-08     Completed Date:  2013-10-01     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1265-76     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Biological Availability
Child
Child, Preschool
Dose-Response Relationship, Drug
Female
Gastroesophageal Reflux / metabolism*,  prevention & control
Gastrointestinal Hemorrhage / metabolism*,  prevention & control
Histamine H2 Antagonists / pharmacokinetics*,  pharmacology
Humans
Infant
Infant, Newborn
Male
Models, Biological
Models, Theoretical
Prospective Studies
Ranitidine / pharmacokinetics*,  pharmacology
Stomach Ulcer / metabolism*,  prevention & control
Chemical
Reg. No./Substance:
0/Histamine H2 Antagonists; 884KT10YB7/Ranitidine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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