RESUMO
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.
Assuntos
Acetamidas , Antidepressivos , Espectrometria de Massas em Tandem , Acetamidas/farmacocinética , Administração Oral , Animais , Antidepressivos/farmacocinética , Área Sob a Curva , Cromatografia Líquida/veterinária , Estudos Cross-Over , Cães , Jejum , Meia-Vida , Espectrometria de Massas em Tandem/veterináriaRESUMO
Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40â¯mg dose of VLZ in healthy Labrador dogs (nâ¯=â¯6) in fasted and fed conditions. Dogs were randomly divided in two (nâ¯=â¯3) groups in a cross-over study design (2â¯×â¯2). Group I was administered with VLZ at 40â¯mg/dog after fasting over-night. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis. VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30â¯min to 10â¯h for the fasted group and 4â¯h to 35â¯h for the fed group. The values for t1/2λz were statistically different between the groups (fed, 4.6⯱â¯1.1â¯h vs fasted, 1.7⯱â¯0.2â¯h). Tmax drastically changed between the groups (fed, 10â¯h vs fasted, 1.5â¯h), while Cmax did not significantly vary (fed, 39.4⯱â¯5.6â¯ng/mL vs fasted, 38.7⯱â¯4.8â¯ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8⯱â¯6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog.