Population Pharmacokinetic Meta‐Analysis of Vortioxetine in Healthy Individuals
Open Access
- 22 May 2014
- journal article
- research article
- Published by Wiley in Basic & Clinical Pharmacology & Toxicology
- Vol. 115 (6), 552-559
- https://doi.org/10.1111/bcpt.12256
Abstract
The objective was to describe the pharmacokinetics of vortioxetine and evaluate the effect of intrinsic and extrinsic factors in the healthy population. Data from 26 clinical pharmacology studies were pooled. A total of 21,758 vortioxetine quantifiable plasma concentrations were collected from 887 subjects with corresponding demography. The doses ranged from 2.5 to 75 mg (single dose) and 2.5–60 mg (multiple QD doses). The pharmacokinetics of vortioxetine was best characterised by a two-compartment model with first-order absorption, lag-time and linear elimination, with interindividual error terms for absorption rate constant, oral clearance and central volume of distribution. The population mean was 32.7 L/hr for oral clearance and 1.97·103 L for the central volume of distribution. The average elimination half-life was 65.8 hr. CYP2D6 inferred metabolic status (ultra, extensive, intermediate or poor metabolisers) and age on oral clearance and height on central volume of distribution were identified as statistically significant covariate–parameter relationships. For CYP2D6 poor metabolisers, CL/F was approximately 50% to that seen in CYP2D6 extensive metabolisers. The impact of height on V2/F and age on CL/F was low and not considered to be clinically relevant. The final model was found to be reliable, stable and predictive. A reliable, stable and predictive pharmacokinetic model was developed to characterise pharmacokinetics of vortioxetine in the healthy population.Keywords
This publication has 13 references indexed in Scilit:
- The Clinical Pharmacokinetics of Lu AA21004 and its Major Metabolite in Healthy Young VolunteersBasic & Clinical Pharmacology & Toxicology, 2012
- Identification of the Cytochrome P450 and Other Enzymes Involved in the In Vitro Oxidative Metabolism of a Novel Antidepressant, Lu AA21004Drug Metabolism and Disposition, 2012
- Current Understanding of Drug Disposition in Kidney DiseaseThe Journal of Clinical Pharmacology, 2012
- Importance of Shrinkage in Empirical Bayes Estimates for Diagnostics: Problems and SolutionsThe AAPS Journal, 2009
- Assessment of the Impact of Renal Impairment on Systemic Exposure of New Molecular Entities: Evaluation of Recent New Drug ApplicationsClinical Pharmacology & Therapeutics, 2008
- Emerging Evidence of the Impact of Kidney Disease on Drug Metabolism and TransportClinical Pharmacology & Therapeutics, 2008
- Diagnosing Model DiagnosticsClinical Pharmacology & Therapeutics, 2007
- Metrics for External Model Evaluation with an Application to the Population Pharmacokinetics of GliclazidePharmaceutical Research, 2006
- Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic applicationPharmacology & Therapeutics, 2006
- The Effect of Renal Failure on Hepatic Drug ClearanceDICP, 1991