Agomelatine is a novel melatonergic antidepressant, with a non-monoaminergic mechanism of action. The aim of this study was to evaluate its plasma concentrations after a single oral dose of 300 mg/dog in fasted and fed status. The research was carried out in 6 adult healthy Labrador dogs according to a randomized open, single-dose, two-treatment, two-phase, paired 2 × 2 cross-over study. At the end of the study all the animals had received the drug in fasted and fed conditions. The drug concentrations were detected in plasma by a validated LC-MS/MS analytical method. The plasma concentrations of agomelatine were found to be extremely variable in both groups as well as the pharmacokinetic profiles. Due to these variable findings the only reliable pharmacokinetic parameters were assessed as Cmax (31.8 vs 15.7 ng/mL), Tmax (0.75 vs 4 h) and AUC (155 vs 52 ng h/mL) in fasted and fed status, respectively. Unfortunately, as a pioneer study, the small animal sample size used along with the unanticipated variability did not allow to neither statistically estimate if food can affect the pharmacokinetics of agomelatine nor recommend agomelatine for off-label therapies in canine species. Further studies are warranted to clarify this issue.

Agomelatine: A novel melatonergic antidepressant. Method validation and first exploratory pharmacokinetic study in fasted and fed dogs

Sartini I.;Poapolathep A.;Giorgi M.
Ultimo
2021-01-01

Abstract

Agomelatine is a novel melatonergic antidepressant, with a non-monoaminergic mechanism of action. The aim of this study was to evaluate its plasma concentrations after a single oral dose of 300 mg/dog in fasted and fed status. The research was carried out in 6 adult healthy Labrador dogs according to a randomized open, single-dose, two-treatment, two-phase, paired 2 × 2 cross-over study. At the end of the study all the animals had received the drug in fasted and fed conditions. The drug concentrations were detected in plasma by a validated LC-MS/MS analytical method. The plasma concentrations of agomelatine were found to be extremely variable in both groups as well as the pharmacokinetic profiles. Due to these variable findings the only reliable pharmacokinetic parameters were assessed as Cmax (31.8 vs 15.7 ng/mL), Tmax (0.75 vs 4 h) and AUC (155 vs 52 ng h/mL) in fasted and fed status, respectively. Unfortunately, as a pioneer study, the small animal sample size used along with the unanticipated variability did not allow to neither statistically estimate if food can affect the pharmacokinetics of agomelatine nor recommend agomelatine for off-label therapies in canine species. Further studies are warranted to clarify this issue.
2021
Lebkowska-Wieruszewska, B.; Ziolkowski, H.; Sartini, I.; Lisowski, A.; Kowalski, C. J.; Poapolathep, A.; Giorgi, M.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1111490
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact