title: Comparison between dried blood spot and plasma sampling for therapeutic drug monitoring of antiepileptic drugs in children with epilepsy: A step towards home sampling.
abstract: OBJECTIVE
  To investigate if dried blood spots could be used for therapeutic drug monitoring of the antiepileptic drugs, carbamazepine, lamotrigine and valproic acid in children with epilepsy.
  
  
  METHODS
  Fingerprick blood samples from 46 children at a neuropediatric outpatient clinic was collected on filterpaper at the same time as capillary plasma sampling. A validated dried blood spot liquid chromatography tandem mass spectrometry method for carbamazepine, lamotrigine and valproic acid was compared with the routine plasma laboratory methods. Method agreement was evaluated and plasma concentrations were estimated by different conversion approaches.
  
  
  RESULTS
  Strong correlation was shown between dried blood spot and plasma concentrations for all three drugs, with R2 values>0.89. Regression analysis showed a proportional bias with 35% lower dried blood spot concentrations for valproic acid (n=33) and concentrations were 18% higher for carbamazepine (n=17). A ratio approach was used to make a conversion from dried blood spots to estimated plasma for these two drugs. Dried blood spot concentrations were directly comparable with plasma for lamotrigine (n=20).
  
  
  CONCLUSIONS
  This study supports that dried blood spot concentrations can be used as an alternative to plasma in a children population for three commonly used antiepileptic drugs with the possibility to expand by adding other antiepileptic drugs. Clinical decisions can be made based on converted (carbamazepine, valproic acid) or unconverted (lamotrigine) dried blood spot concentrations. Dried blood spot sampling, in the future taken at home, will simplify an effective therapeutic drug monitoring for this group of patients who often have concomitant disorders and also reduce costs for society.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: camilla.linder@karolinska.se.
authors.forename: Camilla
authors.initials: C
authors.lastname: Linder
authors.affiliation: Department of Clinical Science, Technology and Intervention (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Wide
authors.affiliation: Department of Clinical Science, Technology and Intervention (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Walander
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafsson
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Pohanka
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D059788:Dried Blood Spot Testing; D016903:Drug Monitoring / Q000379:methods*; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D000927:Anticonvulsants
keywords: Conversion factor; Estimated plasma concentrations; Hematocrit; LC-MS/MS; Red blood cell/plasma ratio