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Dried blood microsampling-based therapeutic drug monitoring of antiepileptic drugs in children with nodding syndrome and epilepsy in Uganda and the Democratic Republic of the Congo

(2020) THERAPEUTIC DRUG MONITORING. 42(3). p.481-490
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Abstract
Nodding syndrome is a highly debilitating, generalized seizure disorder, affecting children in subregions of sub-Saharan Africa. Despite numerous efforts to uncover the etiology, the exact cause of this syndrome still remains obscure. Therefore, to date, patients only receive symptomatic care, including the administration of first-generation antiepileptic drugs for seizure control. As data on the efficacy of drugs within this population are completely lacking, the aim of this study was to explore how therapeutic drug monitoring could help to understand the differential response to therapy. Considering the challenging environment in which sampling had to be performed (remote areas, devoid of electricity, running water, etc), dried blood matrices [ie, dried blood spots (DBSs)] and volumetric absorptive microsampling (VAMS) were considered fit-for-purpose. In addition, owing to the similarities between the syndrome and other forms of epilepsy, samples originating from patients suffering from (onchocerciasis-associated) epilepsy were included. In total, 68 patients with Nodding syndrome from Uganda, 58 Ugandan patients with epilepsy, and 137 patients with onchocerciasis-associated epilepsy from the Democratic Republic of the Congo were included. VAMS samples and DBS were analyzed using validated methods, involving manual extraction or fully automated extraction, respectively, before quantification using liquid chromatography coupled with tandem mass spectrometry. Analysis revealed that serum concentrations (calculated from DBS) within the respective reference ranges were attained in only 52.9% of the 68 Nodding syndrome patients treated with valproic acid, in 21.4% of the 56 Ugandan epilepsy patients treated with carbamazepine, and in 65.7% of the 137 onchocerciasis-associated epilepsy patients from the Democratic Republic of the Congo treated with phenobarbital. In all other instances, concentrations were subtherapeutic. Furthermore, on comparing DBS with VAMS concentrations, an inexplicable overestimation was observed in the latter. Finally, no obvious link could be observed between the obtained drug concentrations and the number of seizures experienced during the last month before sampling, elaborating the fact that the level of improvement in some patients cannot simply be linked to reaching therapeutic concentrations.
Keywords
therapeutic drug monitoring, dried blood spots, volumetric absorptive microsampling, Nodding syndrome, epilepsy, antiepileptics, ONCHOCERCIASIS-ASSOCIATED EPILEPSY, MARIDI COUNTY, SPOT, GUIDELINES, VILLAGES

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Citation

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MLA
Velghe, Sofie, et al. “Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children with Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo.” THERAPEUTIC DRUG MONITORING, vol. 42, no. 3, 2020, pp. 481–90, doi:10.1097/FTD.0000000000000720.
APA
Velghe, S., Delahaye, L., Ogwang, R., Hotterbeekx, A., Colebunders, R., Mandro, M., … Stove, C. (2020). Dried blood microsampling-based therapeutic drug monitoring of antiepileptic drugs in children with nodding syndrome and epilepsy in Uganda and the Democratic Republic of the Congo. THERAPEUTIC DRUG MONITORING, 42(3), 481–490. https://doi.org/10.1097/FTD.0000000000000720
Chicago author-date
Velghe, Sofie, Lisa Delahaye, Rodney Ogwang, An Hotterbeekx, Robert Colebunders, Michel Mandro, Richard Idro, and Christophe Stove. 2020. “Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children with Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo.” THERAPEUTIC DRUG MONITORING 42 (3): 481–90. https://doi.org/10.1097/FTD.0000000000000720.
Chicago author-date (all authors)
Velghe, Sofie, Lisa Delahaye, Rodney Ogwang, An Hotterbeekx, Robert Colebunders, Michel Mandro, Richard Idro, and Christophe Stove. 2020. “Dried Blood Microsampling-Based Therapeutic Drug Monitoring of Antiepileptic Drugs in Children with Nodding Syndrome and Epilepsy in Uganda and the Democratic Republic of the Congo.” THERAPEUTIC DRUG MONITORING 42 (3): 481–490. doi:10.1097/FTD.0000000000000720.
Vancouver
1.
Velghe S, Delahaye L, Ogwang R, Hotterbeekx A, Colebunders R, Mandro M, et al. Dried blood microsampling-based therapeutic drug monitoring of antiepileptic drugs in children with nodding syndrome and epilepsy in Uganda and the Democratic Republic of the Congo. THERAPEUTIC DRUG MONITORING. 2020;42(3):481–90.
IEEE
[1]
S. Velghe et al., “Dried blood microsampling-based therapeutic drug monitoring of antiepileptic drugs in children with nodding syndrome and epilepsy in Uganda and the Democratic Republic of the Congo,” THERAPEUTIC DRUG MONITORING, vol. 42, no. 3, pp. 481–490, 2020.
@article{8687073,
  abstract     = {{Nodding syndrome is a highly debilitating, generalized seizure disorder, affecting children in subregions of sub-Saharan Africa. Despite numerous efforts to uncover the etiology, the exact cause of this syndrome still remains obscure. Therefore, to date, patients only receive symptomatic care, including the administration of first-generation
antiepileptic drugs for seizure control. As data on the efficacy of drugs within this population are completely lacking, the aim of this study was to explore how therapeutic drug monitoring could help to understand the
differential response to therapy. Considering the challenging environment in which sampling had to be performed (remote areas, devoid of electricity, running water, etc), dried blood matrices [ie, dried blood spots (DBSs)] and volumetric absorptive microsampling (VAMS) were considered fit-for-purpose. In addition, owing to the similarities between the syndrome and other forms of epilepsy, samples originating from patients suffering from (onchocerciasis-associated) epilepsy were included. In total, 68 patients with Nodding syndrome from Uganda,
58 Ugandan patients with epilepsy, and 137 patients with onchocerciasis-associated epilepsy from the Democratic Republic of the Congo were included. VAMS samples and DBS were analyzed using validated methods, involving manual extraction or fully automated extraction, respectively, before quantification using liquid chromatography coupled with tandem mass spectrometry. Analysis revealed that serum concentrations (calculated from DBS) within the respective reference ranges were attained in only 52.9% of the 68 Nodding syndrome patients treated with valproic acid, in 21.4% of the 56 Ugandan epilepsy patients treated with carbamazepine, and in 65.7% of the 137 onchocerciasis-associated epilepsy patients from the Democratic Republic of the Congo treated with phenobarbital. In all other instances, concentrations were subtherapeutic. Furthermore, on comparing DBS with VAMS concentrations, an inexplicable overestimation was observed in the latter. Finally, no obvious link could be observed
between the obtained drug concentrations and the number of seizures experienced during the last month before sampling, elaborating the fact that the level of improvement in some patients cannot simply be linked
to reaching therapeutic concentrations.}},
  author       = {{Velghe, Sofie and Delahaye, Lisa and Ogwang, Rodney and Hotterbeekx, An and Colebunders, Robert and Mandro, Michel and Idro, Richard and Stove, Christophe}},
  issn         = {{0163-4356}},
  journal      = {{THERAPEUTIC DRUG MONITORING}},
  keywords     = {{therapeutic drug monitoring,dried blood spots,volumetric absorptive microsampling,Nodding syndrome,epilepsy,antiepileptics,ONCHOCERCIASIS-ASSOCIATED EPILEPSY,MARIDI COUNTY,SPOT,GUIDELINES,VILLAGES}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{481--490}},
  title        = {{Dried blood microsampling-based therapeutic drug monitoring of antiepileptic drugs in children with nodding syndrome and epilepsy in Uganda and the Democratic Republic of the Congo}},
  url          = {{http://doi.org/10.1097/FTD.0000000000000720}},
  volume       = {{42}},
  year         = {{2020}},
}

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