Therapeutic drug monitoring of levetiracetam - Is dried blood spot sampling suitable?

Abstract

Background: Therapeutic drug monitoring helps prevent seizures and minimize side effects in epilepsy patients. Phlebotomy is the gold standard for blood collection but can be difficult for children, pregnant women, and patients in remote areas. We previously validated dried blood spot (DBS) sampling for carbamazepine, lamotrigine, levetiracetam (LEV), and valproic acid. Uncertainties in LEV comparisons from the previous validation were further investigated in this study by increasing sample numbers and comparing results using both immunochemistry and LC-MS/MS methods. Additionally, capillary and venous DBS were compared, and the stability of samples during mail transport was assessed.

Aim: To compare LEV concentrations in capillary DBS and plasma, and to assess the stability of capillary DBS during transportation.

Method: Capillary and venous blood samples were collected from 40 LEV-treated patients. Concentrations were measured using immunochemistry and liquid chromatography tandem mass spectrometry methods. Comparisons between matrices and methods were analyzed with Passing-Bablok regression and Bland-Altman plots.

Results: No proportional bias was found in regression analysis and Bland-Altman plots showed no bias between methods. For capillary DBS versus plasma concentrations, 92.1 % of values were within 20 % of the mean. No bias was detected between capillary and venous DBS, with deviations within acceptable limits. Sample stability was maintained during mail transport.

Conclusion: The concentrations obtained for LEV in capillary DBS versus plasma showed that therapeutic drug monitoring of LEV can be performed as at-home self-sampling with DBS mailed to the laboratory for analysis.