The pharmacokinetics of escitalopram in patients with hepatic impairment
Journal Title: The AAPS Journal - Year 2006, Vol 8, Issue 1
Abstract
The effect of hepatic impairment on the pharmacokinetics of escitalopram was determined by means of nonlinear mixed effect modeling, considering both the Child-Pugh classification (and its components) and cytochrome P450 2C19 (CYP2C19) activity. Twenty-four subjects were grouped according to their Child-Pugh score as healthy, with mild hepatic impairment or with moderate hepatic impairment. The subjects were administered a single oral dose of escitalopram 20 mg, and blood was sampled up to 168 hours after dosage. The serum concentration of escitalopram was determined and the pharmacokinetics assessed by nonlinear mixed effect modeling. The CYP2C19 activity was measured from the urinary excretion ratio of S/R-mephenytoin. All subjects tolerated the treatment well, and no serious adverse events were reported. Predicted mean area under the curve from zero to infinity (AUCinf) values were 51% and 69% higher for patients with mild and moderate hepatic impairment (Child-Pugh classification), respectively, compared with healthy subjects. The best-fitting model showed an influence of CYP2C19 activity on clearance and body weight on the volume of distribution for escitalopram. CYP2C19 activity is a better predictor of escitalopram clearance than is Child-Pugh classification.
Authors and Affiliations
Johan Areberg, Jacob Strøyer Christophersen, Mette Nøhr Poulsen, Frank Larsen, Karl-Heinz Molz
Keywords
Related Articles
- EP ID EP681633
- DOI 10.1208/aapsj080102
- Views 78
- Downloads 0
Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology
Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight “peptidome” is an attractive information archive...
A Systematic Analysis of the Sensitivity of Plasma Pharmacokinetics to Detect Differences in the Pulmonary Performance of Inhaled Fluticasone Propionate Products Using a Model-Based Simulation Approach
The online version of this article (doi:10.1208/s12248-015-9768-y) contains supplementary material, which is available to authorized users.
Concluding summary: Proceedings of the AAPS Biotec Open Forum on “Aggregation of Protein Therapeutics”
Transporter and ion channel gene expression after caco-2 cell differentiation using 2 different microarray technologies
mRNA expression profiles had previously been measured in Caco-2 cells (human colonic carcinoma cells) using either custom-designed spotted oligonucleotide arrays or Affymetrix GeneChip oligonucleotide arrays. The Caco-2...
Specificity and selectivity evaluations of ligand binding assay of protein therapeutics against concomitant drugs and related endogenous proteins