Prophylactic ranitidine treatment in critically ill children - a population pharmacokinetic study
Data(s) |
01/05/2013
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Resumo |
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 32.1lh for total clearance and 285l for volume of distribution, both allometrically modelled for a 70kg adult. Final estimates for absorption rate constant and bioavailability were 1.31h 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. |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Hawwa , A F , Westwood , P M , Collier , P S , Millership , J S , Yakkundi , S , Thurley , G , Shields , M D , Nunn , A J , Halliday , H L & McElnay , J C 2013 , ' Prophylactic ranitidine treatment in critically ill children - a population pharmacokinetic study ' British Journal of Clinical Pharmacology , vol 75 , no. 5 , pp. 1265-1276 . DOI: 10.1111/j.1365-2125.2012.04473.x |
Tipo |
article |