Population Pharmacokinetics of Valsartan in Pediatrics
2009
Summary: The objective of this work was to develop a population pharmacokinetic model to assess the influence of subject covariates on the pharmacokinetics of valsartan in children. Data were collected from a single dose study in 26 hypertensive children ages 1 to 16 years. Subjects received 2 mg/kg valsartan suspension up to a maximum dose of 80 mg. Plasma samples were collected and analyzed using LC/MS/MS. Several structural pharmacokinetic models were evaluated for appropriateness. Allometric scaling and standard covariate analyses were performed to explain interindividual variabilities. Objective function values and goodness of fit plots were used for model selection. A posterior predictive check was used for model evaluation. A linear 2-compartment first-order elimination model with zero-order absorption and lag-time best described the disposition of valsartan. Allometric scaling and standard covariate analysis revealed that age and body size have similar influence; however, after adjustment for body size using fat free mass (FFM), the effect of increasing age was no longer significant on valsartan clearance (2% per year relative to a typical 8 year old with FFM of 30 kg). The population pharmacokinetic model reveals that increase in age has minimal influence on body size dependent clearance of valsartan in children.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
24
References
12
Citations
NaN
KQI