Comparison of Dried Blood Spots Versus Conventional Plasma Collection for the Characterization of Efavirenz Pharmacokinetics in a Large-Scale Global Clinical Trial-The ENCORE1 Study.

Amara, Alieu B, Else, Laura J, Carey, Dianne, Khoo, Saye, Back, David J, Amin, Janaki, Emery, Sean and Puls, Rebekah L (2017) Comparison of Dried Blood Spots Versus Conventional Plasma Collection for the Characterization of Efavirenz Pharmacokinetics in a Large-Scale Global Clinical Trial-The ENCORE1 Study. Therapeutic drug monitoring, 39 (6). 654 - 658.

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Abstract

The aim of this study was to determine the utility of dried blood spots (DBS) compared with conventional plasma collection methods for characterization of efavirenz pharmacokinetics, in the setting of a large-scale, global clinical trial (ENCORE1).Six hundred thirty patients were recruited from 38 sites and had single matched whole blood DBS and plasma samples (mid-dose interval) taken at weeks 4 and 12 of treatment. In addition, a subgroup of patients underwent intensive DBS and plasma sampling (0-24 hours) to provide full-profile data for pharmacokinetic parameters. Efavirenz concentrations were determined by validated high-performance liquid chromatography-mass spectrometry methods. A DBS-predicted plasma concentration was derived and linear regression and Bland-Altman plots were used to compare DBS-predicted plasma concentrations with that of measured plasma concentrations.Efavirenz DBS and plasma concentrations were significantly correlated (R = 0.904, P < 0.001; n = 1094), and DBS concentrations were, on average, 53% ± 9.5% lower than plasma. In the main study, the DBS-predicted plasma values significantly underestimated the true measured concentration of efavirenz in plasma; the mean difference (95% confidence interval) between efavirenz DBS-predicted concentrations and measured plasma concentrations was -0.451 mg/L (-0.504 to -0.398) at week 4 (n = 561). However, in the intensive study, the mean difference was only 0.086 mg/L (-0.006 to 0.178) at 12 hours after dose (n = 46) and was not statistically significant.Our data show a high correlation between measurements of efavirenz concentrations in plasma and in DBS. However, DBS concentrations significantly underestimated the true measured plasma concentrations in the sparse samples taken in this large multinational ENCORE1 trial.

Item Type:	Article
Uncontrolled Keywords:	Humans, Benzoxazines, Reverse Transcriptase Inhibitors, Drug Monitoring, Specimen Handling, Chromatography, High Pressure Liquid, Linear Models, Double-Blind Method, Time Factors, Female, Male, Tandem Mass Spectrometry, Dried Blood Spot Testing
Depositing User:	Symplectic Admin
Date Deposited:	10 Nov 2017 10:34
Last Modified:	19 Jan 2023 06:50
DOI:	10.1097/ftd.0000000000000448
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3011883

Available Versions of this Item

• Comparison of Dried Blood Spots Versus Conventional Plasma Collection for the Characterization of Efavirenz Pharmacokinetics in a Large-Scale Global Clinical Trial-The ENCORE1 Study. (deposited 10 Nov 2017 10:34) [Currently Displayed]
  • Comparison of Dried Blood Spots Versus Conventional Plasma Collection for the Characterization of Efavirenz Pharmacokinetics in a Large-Scale Global Clinical Trial-The ENCORE1 Study. (deposited 07 Jan 2019 13:50)