INTRODUCTION Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic or antiphlogistic effects labelled for humans. It does not induce the side effects associated with the classical drugs used as pain relievers (NSAIDs and opioids). The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy donkeys. MATERIALS AND METHODS Six Amiata breed adult jennies were randomly assigned to two treatment groups using an open, 2 9 2 Latin-square crossover study design. Group 1 (n = 3) received a single dose of 1 mg kg 1 of FLU injected IV (Katadolon 100 mg 3 ml 1 vial, FLU D-gluconate) into the jugular vein. Group 2 (n = 3) received FLU (5 mg kg 1) via nasogastric tube (Efiret 100 mg hard capsules, FLU maleate). The wash out period was 1-week. Blood samples (5 ml) were collected at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was then analysed by a validated HPLC method. Drug plasma concentration versus time curves were modeled for each subject using a two-compartment open model. RESULTS AND CONCLUSIONS No behavioral changes or alterations in health parameters were observed in the IV and PO groups of animals during or after (up to 7 days) the drug administration. Physiological signs and parameters were normal. After IV and PO administrations, FLU was detectable in plasma for up to 24 h. The mean elimination half-life was longer after PO (10.81 h) than after IV (0.90 h) administration. The Tmax found in this study (0.33 h) was shorter than the Tmax reported for dogs (1.42 h) (1), humans (range 1.6–1.8 h) (2), and cats (2.78 h) (3) showing a faster rate of absorption of the drug in donkeys. A number of factors may be responsible for this difference: the large variation in this parameter in the donkey, different absorption, gastric emptying, transit time or other species-specific factors. The clearance was 4812.8 ml h kg 1 and the AUC was small, findings consistent with a low oral bioavailability of about 20%. The pharmacokinetic trend of FLU in donkeys was different from those earlier reported in cats and dogs where the oral bioavailability was 40%. Surprisingly, the oral bioavailability of FLU in donkeys was much smaller than that reported in horses (70%) (M. Giorgi personal communication). This might be triggered by the faster clearance value in donkeys compared to horses (411 ml h kg 1) rather than a poor drug absorption (Cmax 937 versus 1639 ng ml 1). Further studies are needed to understand if this active ingredient may be used in donkeys.

FLUPIRTINE: INTRAVENOUS AND ORAL PHARMACOKINETICS IN THE DONKEY

GIORGI, MARIO;
2015

Abstract

INTRODUCTION Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic or antiphlogistic effects labelled for humans. It does not induce the side effects associated with the classical drugs used as pain relievers (NSAIDs and opioids). The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy donkeys. MATERIALS AND METHODS Six Amiata breed adult jennies were randomly assigned to two treatment groups using an open, 2 9 2 Latin-square crossover study design. Group 1 (n = 3) received a single dose of 1 mg kg 1 of FLU injected IV (Katadolon 100 mg 3 ml 1 vial, FLU D-gluconate) into the jugular vein. Group 2 (n = 3) received FLU (5 mg kg 1) via nasogastric tube (Efiret 100 mg hard capsules, FLU maleate). The wash out period was 1-week. Blood samples (5 ml) were collected at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36 and 48 h and plasma was then analysed by a validated HPLC method. Drug plasma concentration versus time curves were modeled for each subject using a two-compartment open model. RESULTS AND CONCLUSIONS No behavioral changes or alterations in health parameters were observed in the IV and PO groups of animals during or after (up to 7 days) the drug administration. Physiological signs and parameters were normal. After IV and PO administrations, FLU was detectable in plasma for up to 24 h. The mean elimination half-life was longer after PO (10.81 h) than after IV (0.90 h) administration. The Tmax found in this study (0.33 h) was shorter than the Tmax reported for dogs (1.42 h) (1), humans (range 1.6–1.8 h) (2), and cats (2.78 h) (3) showing a faster rate of absorption of the drug in donkeys. A number of factors may be responsible for this difference: the large variation in this parameter in the donkey, different absorption, gastric emptying, transit time or other species-specific factors. The clearance was 4812.8 ml h kg 1 and the AUC was small, findings consistent with a low oral bioavailability of about 20%. The pharmacokinetic trend of FLU in donkeys was different from those earlier reported in cats and dogs where the oral bioavailability was 40%. Surprisingly, the oral bioavailability of FLU in donkeys was much smaller than that reported in horses (70%) (M. Giorgi personal communication). This might be triggered by the faster clearance value in donkeys compared to horses (411 ml h kg 1) rather than a poor drug absorption (Cmax 937 versus 1639 ng ml 1). Further studies are needed to understand if this active ingredient may be used in donkeys.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/751251
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