| Population pharmacokinetics and Bayesian estimator of mycophenolic acid in children with idiopathic nephrotic syndrome. | |
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MedLine Citation:
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PMID: 20406220 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC(0-12)). METHODS: The pharmacokinetic model of MMF was described from 23 patients aged 7.4 +/- 3.9 years (range 2.9-14.9) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with lag-time and first-order absorption and elimination was developed. The final model was validated using visual predictive check. Bayesian estimator was validated using circular permutation method. RESULTS: The population pharmacokinetic parameters were apparent oral clearance 9.7 l h(-1), apparent central volume of distribution 22.3 l, apparent peripheral volume of distribution 250 l, inter-compartment clearance 18.8 l h(-1), absorption rate constant 5.16 h(-1), lag time 0.215 h. The covariate analysis identified body weight and serum albumin as individual factors influencing the apparent oral clearance. Accurate Bayesian estimation of AUC(0-12) was obtained using the combination of three MPA concentrations measured just before (T(0)), 1 and 4 h (T(1) and T(4)) after drug intake with a small error of 0.298 microg h(-1) ml(-1) between estimated and reference AUC(0-12). CONCLUSIONS: The population pharmacokinetic model of MPA was developed in children with INS. A three-point (T(0), T(1) and T(4)h) Bayesian estimator of AUC(0-12) was developed and might be used to investigate the relation between MPA pharmacokinetic and pharmacodynamics in children with INS and determine if there is any indication to monitor MPA exposure in order to improve patient outcome based on individual AUC-controlled MMF dosing. |
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Authors:
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Wei Zhao; Valéry Elie; Véronique Baudouin; Albert Bensman; Jean Luc André; Karine Brochard; Françoise Broux; Mathilde Cailliez; Chantal Loirat; Evelyne Jacqz-Aigrain |
Publication Detail:
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Type: Clinical Trial; Journal Article; Multicenter Study |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: 69 ISSN: 1365-2125 ISO Abbreviation: Br J Clin Pharmacol Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-21 Completed Date: 2010-08-02 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 358-66 Citation Subset: IM |
Affiliation:
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Department of Paediatric Pharmacology and Pharmacogenetics, Clinical Investigation Centre INSERM, Hôpital Robert Debré, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Adolescent Area Under Curve Bayes Theorem Child Child, Preschool Chromatography, High Pressure Liquid Enzyme Inhibitors / blood, pharmacokinetics* Female Humans Immunosuppressive Agents / pharmacokinetics*, therapeutic use Male Models, Biological Mycophenolic Acid / analogs & derivatives*, blood, pharmacokinetics*, therapeutic use Nephrotic Syndrome / drug therapy* Prospective Studies |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Immunosuppressive Agents; 128794-94-5/mycophenolate mofetil; 24280-93-1/Mycophenolic Acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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