Objective: To compare the pharmacokinetic profiles of FLU after IV and PO administration in healthy cats, dogs, donkeys and horses. Species specific differences might affect the optimal dose of drugs. Materials & Methods: Six healthy cats, dogs, donkey and horses, were allocated to four 2x2 latin square crossover studies (two-equal random treatment groups for each study). Blood was collected at predetermined times within 24 h and plasma was analysed by a validated HPLC FL method. No behavioural changes or alterations in health parameters were observed in the IV or IM groups of animals during or after (up to 7 days) the drug administration. Results & Conclusion: Cats and dogs showed similar pharmacokinetic profiles with a similar oral bioavailability (around 40%). Large difference were found in the pharmacokinetic parameters between horses and donkeys with a bioavailability of 70 and 20%, respectively. The flupirtine half life in donkeys was short. After multiple dose simulations and modelling the theoretical minimal effective concentrations (MEC) for each species were calculated according to the human clinical dose. In the donkey due to the fast pharmacokinetic of flupirtine, this calculation was not possible. An oral dose of 2.6, 3.2 and 1.3 mg/kg were calculated to give Cmax and AUC values in horses, dogs and cats, respectively, similar to those reported in humans after a clinical dose administration with a theoretical FLU effective plasma concentration of 187, 93, 111 and ng/mL, respectively.

COMPARATIVE PHARMACOKINETICS OF THE ANALGESIC DRUG FLUPIRTINE IN DIFFERENT ANIMAL SPECIES

GIORGI, MARIO;
2016

Abstract

Objective: To compare the pharmacokinetic profiles of FLU after IV and PO administration in healthy cats, dogs, donkeys and horses. Species specific differences might affect the optimal dose of drugs. Materials & Methods: Six healthy cats, dogs, donkey and horses, were allocated to four 2x2 latin square crossover studies (two-equal random treatment groups for each study). Blood was collected at predetermined times within 24 h and plasma was analysed by a validated HPLC FL method. No behavioural changes or alterations in health parameters were observed in the IV or IM groups of animals during or after (up to 7 days) the drug administration. Results & Conclusion: Cats and dogs showed similar pharmacokinetic profiles with a similar oral bioavailability (around 40%). Large difference were found in the pharmacokinetic parameters between horses and donkeys with a bioavailability of 70 and 20%, respectively. The flupirtine half life in donkeys was short. After multiple dose simulations and modelling the theoretical minimal effective concentrations (MEC) for each species were calculated according to the human clinical dose. In the donkey due to the fast pharmacokinetic of flupirtine, this calculation was not possible. An oral dose of 2.6, 3.2 and 1.3 mg/kg were calculated to give Cmax and AUC values in horses, dogs and cats, respectively, similar to those reported in humans after a clinical dose administration with a theoretical FLU effective plasma concentration of 187, 93, 111 and ng/mL, respectively.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/813755
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