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Estimation of the optimal dosing regimen of escitalopram in dogs : a dose occupancy study with [11C]DASB

Olivia Taylor, Nick Van Laeken (UGent) , Ingeborgh Polis (UGent) , Robrecht Dockx (UGent) , Lise Vlerick (UGent) , André Dobbeleir, Ingeborg Goethals (UGent) , Jimmy Saunders (UGent) , Nele Sadones (UGent) , Chris Baeken (UGent) , et al.
(2017) PLOS ONE. 12(6).
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The integrative neuroscience of behavioral control (Neuroscience)
Abstract
Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i. v. injection 0.83 mg/ kg. Blood samples were taken up to 12 hours after i. v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.
Keywords
POSITRON-EMISSION-TOMOGRAPHY, SEROTONIN TRANSPORTER, CITALOPRAM

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Chicago
Taylor, Olivia, Nick Van Laeken, Ingeborgh Polis, Robrecht Dockx, Lise Vlerick, André Dobbeleir, Ingeborg Goethals, et al. 2017. “Estimation of the Optimal Dosing Regimen of Escitalopram in Dogs : a Dose Occupancy Study with [11C]DASB.” Plos One 12 (6).
APA
Taylor, O., Van Laeken, N., Polis, I., Dockx, R., Vlerick, L., Dobbeleir, A., Goethals, I., et al. (2017). Estimation of the optimal dosing regimen of escitalopram in dogs : a dose occupancy study with [11C]DASB. PLOS ONE, 12(6).
Vancouver
1.
Taylor O, Van Laeken N, Polis I, Dockx R, Vlerick L, Dobbeleir A, et al. Estimation of the optimal dosing regimen of escitalopram in dogs : a dose occupancy study with [11C]DASB. PLOS ONE. 2017;12(6).
MLA
Taylor, Olivia, Nick Van Laeken, Ingeborgh Polis, et al. “Estimation of the Optimal Dosing Regimen of Escitalopram in Dogs : a Dose Occupancy Study with [11C]DASB.” PLOS ONE 12.6 (2017): n. pag. Print.
@article{8528711,
  abstract     = {Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80\% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i. v. injection 0.83 mg/ kg. Blood samples were taken up to 12 hours after i. v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80\% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.},
  articleno    = {e0179927},
  author       = {Taylor, Olivia and Van Laeken, Nick and Polis, Ingeborgh and Dockx, Robrecht and Vlerick, Lise and Dobbeleir, Andr{\'e} and Goethals, Ingeborg and Saunders, Jimmy and Sadones, Nele and Baeken, Chris and De Vos, Filip and Peremans, Kathelijne},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {POSITRON-EMISSION-TOMOGRAPHY,SEROTONIN TRANSPORTER,CITALOPRAM},
  language     = {eng},
  number       = {6},
  pages        = {11},
  title        = {Estimation of the optimal dosing regimen of escitalopram in dogs : a dose occupancy study with [11C]DASB},
  url          = {http://dx.doi.org/10.1371/journal.pone.0179927},
  volume       = {12},
  year         = {2017},
}

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