Objective: Mirtazapine (MRT) is a human antidepressant drug mainly metabolized by the cytochrome P450 enzyme system to 8-OH mirtazapine (8-OH) and to dimetilmirtazapine (DMR). Anecdotal clinical observations suggested doses for dogs be extrapolated from human doses, but no pharmacological studies have been reported to date to support these speculations. The aim of this study was to assess the pharmacokinetics of MRT and its metabolites DMT and 8-OH to provide useful information to improve the knowledge of this drug in canine species. Materials & Methods: The subjects were six healthy male Beagle dogs, aged from 1-2 years and weighing between 15 and 17 Kg. Animals were administered MRT (20 mg/tablet/dog) under fasting conditions. This dose was determined based on anecdotal evidence indicating an effective dose rate of about 1 mg/kg. A catheter was inserted into the right cephalic vein to withdrawal a blood sample at determined times after drug administration. Plasma MRT and metabolite concentrations were evaluated by HPLC-FL detection method re-validated in canine plasma according the following parameters: linearity, sensitivity, selectivity and accuracy. Results & Conclusion: MRT and DMR were quantified in plasma from 0.25 up to 10 h, while 8-OH was quantified from 0.50 up to 10 h. The 8-OH metabolite demonstrated the highest plasma concentration. The present study indicated that MRT has a different pharmacokinetic profile in dogs compared to that in cats and humans and caution should be paid when extrapolating doses from other species. In veterinary medicine, MRT is likely to have more applications than other drugs currently available for veterinary use, many of these are only utilised for separation anxiety disorder in dogs (clomipramine, fluoxetine and trazodone). Compared with the pharmacokinetic profiles of these drugs, MRT shows a longer mean resident time and a shorter Tmax. These properties could be beneficial in instances of accidental overdose where the expected cardio-toxic side effects and serotonin syndrome could be mitigated for this medication. The antagonism of 5-HT3 receptor by MRT may also result in an anti-emetic therapeutic effect. Its use as analgesic agent due to its effects on noradrenergic and serotonic system has been also speculated. This preliminary data could be useful in prospective studies involving MRT in canine species.
MIRTAZAPINE IN BEAGLE DOGS
GIORGI, MARIO;
2011-01-01
Abstract
Objective: Mirtazapine (MRT) is a human antidepressant drug mainly metabolized by the cytochrome P450 enzyme system to 8-OH mirtazapine (8-OH) and to dimetilmirtazapine (DMR). Anecdotal clinical observations suggested doses for dogs be extrapolated from human doses, but no pharmacological studies have been reported to date to support these speculations. The aim of this study was to assess the pharmacokinetics of MRT and its metabolites DMT and 8-OH to provide useful information to improve the knowledge of this drug in canine species. Materials & Methods: The subjects were six healthy male Beagle dogs, aged from 1-2 years and weighing between 15 and 17 Kg. Animals were administered MRT (20 mg/tablet/dog) under fasting conditions. This dose was determined based on anecdotal evidence indicating an effective dose rate of about 1 mg/kg. A catheter was inserted into the right cephalic vein to withdrawal a blood sample at determined times after drug administration. Plasma MRT and metabolite concentrations were evaluated by HPLC-FL detection method re-validated in canine plasma according the following parameters: linearity, sensitivity, selectivity and accuracy. Results & Conclusion: MRT and DMR were quantified in plasma from 0.25 up to 10 h, while 8-OH was quantified from 0.50 up to 10 h. The 8-OH metabolite demonstrated the highest plasma concentration. The present study indicated that MRT has a different pharmacokinetic profile in dogs compared to that in cats and humans and caution should be paid when extrapolating doses from other species. In veterinary medicine, MRT is likely to have more applications than other drugs currently available for veterinary use, many of these are only utilised for separation anxiety disorder in dogs (clomipramine, fluoxetine and trazodone). Compared with the pharmacokinetic profiles of these drugs, MRT shows a longer mean resident time and a shorter Tmax. These properties could be beneficial in instances of accidental overdose where the expected cardio-toxic side effects and serotonin syndrome could be mitigated for this medication. The antagonism of 5-HT3 receptor by MRT may also result in an anti-emetic therapeutic effect. Its use as analgesic agent due to its effects on noradrenergic and serotonic system has been also speculated. This preliminary data could be useful in prospective studies involving MRT in canine species.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
