Population pharmacokinetics of atorvastatin and its active metabolites in children and adolescents with heterozygous familial hypercholesterolemia: selective use of informative prior distributions from adults.
|
| Abstract |
The population pharmacokinetics (PPK) of atorvastatin and its principal active metabolite, o-hydroxyatorvastatin, were described in 6-17 years old pediatric hypercholesterolemia patients with a 2-compartment model for both parent and metabolite. Informative prior distributions on selected parameters, based on adult data, were required to stabilize the model and were implemented using a Bayesian penalty term on the likelihood function in the nonlinear mixed effects model (NONMEM VI with PRIOR). Concentrations below the limit of quantitation were treated as censored data using a conditional likelihood function. Atorvastatin apparent oral clearance (CL/F) was described as a function of body weight using an allometric equation. Based on the final model, the typical CL/F estimates for a Tanner Stage 1 patient (35 kg weight) and Tanner Stage ≥2 (50 kg weight), would be 553 and 543 L/hour, respectively. When scaled allometrically, CL/F was similar to values reported for adults. Variability in atorvastatin PK was primarily affected by weight.
|
|---|---|
| Authors | William Knebel, Marc R Gastonguay, Bimal Malhotra, Ahmed El-Tahtawy, Frank Jen, Kuan Gandelman |
| Journal | Journal of clinical pharmacology (J Clin Pharmacol) Vol. 53 Issue 5 Pg. 505-16 (May 2013) ISSN: 1552-4604 [Electronic] England |
| PMID | 23381936 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © The Author(s) 2013. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!