Flupirtine (FLU) is a non-opioid analgesic drug without antipyretic or antiphlogistic effects used in the treatment of a wide range of pain states in human beings. There is a substantial evidence on the efficacy of FLU in humans however this is inadequate to recommend its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy cats. The Animal Welfare Committee of the University of Lublin approved the study protocol. Cats (n=6) were randomly assigned to two treatment groups, using an open, single-dose, two-treatment, two-phase, paired, cross-over design. All cats were fasted for 12 h overnight before each experiment. During the first phase each cat in group 1 (n = 3) received a single dose of 5 mg/kg of FLU (Katadolon®, AWD Pharma) injected IV into the jugular vein. Group 2 (n = 3) received the same dose via PO route (Efiret®, Meda Pharma). A 1- week wash out period was observed. Blood samples were collected at assigned times and plasma was analyzed according to a previous HPLC method (De Vito et al., accepted). The pharmacokinetic calculations were carried out using WinNonLin v 5.3 (Pharsight). A weighting (1/[actual plasma concentration]2) was used. The HPLC method was re-validated in the cat plasma. Briefly, FLU was linear (r2 >0.99) in the range 10-2000 ng/mL. The intraday repeatability was lower than 6.1 %, whereas accuracy, was lower than 5.9 %. No adverse effects at the point of injection and no behavioral or health alterations were observed in the animals during or after (up to 7 days) the study. A bi-compartmental model best fitted the plasma concentrations after IV and PO administrations in all the 6 cats. The average plasma concentration vs. time curves after both the administrations are reported in Fig. 1. After IV administration FLU plasma concentration was largely variable, especially at the first points of collections. FLU was detectable in plasma up to 36 h, then at 48 h the drug concentrations dropped down the LOQ of the method. After oral administration the FLU plasma concentrations were lower than after IV route, but detectable in the same range of time. The Cmax (2460 ng/mL) was shown at a Tmax of (2.78 h). The oral bioavailability (F%) was 39.3 ± 9.7%. The HL of elimination (B_HL) values after either routes were similar. The terminal part of both mean pharmacokinetic curves showed a similar trend of elimination. This is the first study concerning FLU in animal species of veterinary interest. The pharmacokinetic profiles of FLU in cats were somewhat different compared to the FLU disposition in humans. Its PO F% was about 39%. This study could pave the road for the use of this active ingredient in the veterinary field. Further studies need to be undertaken to assess if this drug may be adequate in feline medicine.
Pharmacokinetics of flupirtine in healthy cats following oral and intravenous administrations / DE VITO, Virginia; Lebkowska Wieruszewska, B; Shaban, A; Kowalski, Cj; Giorgi, M.. - (2014). (Intervento presentato al convegno LXVIII Congress S.I.S.VET, SICV, XI Congress aipvet, XII Congress sira tenutosi a Pisa, Italy, nel June 16 th-18th, 2014).
Pharmacokinetics of flupirtine in healthy cats following oral and intravenous administrations.
DE VITO, Virginia;
2014-01-01
Abstract
Flupirtine (FLU) is a non-opioid analgesic drug without antipyretic or antiphlogistic effects used in the treatment of a wide range of pain states in human beings. There is a substantial evidence on the efficacy of FLU in humans however this is inadequate to recommend its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy cats. The Animal Welfare Committee of the University of Lublin approved the study protocol. Cats (n=6) were randomly assigned to two treatment groups, using an open, single-dose, two-treatment, two-phase, paired, cross-over design. All cats were fasted for 12 h overnight before each experiment. During the first phase each cat in group 1 (n = 3) received a single dose of 5 mg/kg of FLU (Katadolon®, AWD Pharma) injected IV into the jugular vein. Group 2 (n = 3) received the same dose via PO route (Efiret®, Meda Pharma). A 1- week wash out period was observed. Blood samples were collected at assigned times and plasma was analyzed according to a previous HPLC method (De Vito et al., accepted). The pharmacokinetic calculations were carried out using WinNonLin v 5.3 (Pharsight). A weighting (1/[actual plasma concentration]2) was used. The HPLC method was re-validated in the cat plasma. Briefly, FLU was linear (r2 >0.99) in the range 10-2000 ng/mL. The intraday repeatability was lower than 6.1 %, whereas accuracy, was lower than 5.9 %. No adverse effects at the point of injection and no behavioral or health alterations were observed in the animals during or after (up to 7 days) the study. A bi-compartmental model best fitted the plasma concentrations after IV and PO administrations in all the 6 cats. The average plasma concentration vs. time curves after both the administrations are reported in Fig. 1. After IV administration FLU plasma concentration was largely variable, especially at the first points of collections. FLU was detectable in plasma up to 36 h, then at 48 h the drug concentrations dropped down the LOQ of the method. After oral administration the FLU plasma concentrations were lower than after IV route, but detectable in the same range of time. The Cmax (2460 ng/mL) was shown at a Tmax of (2.78 h). The oral bioavailability (F%) was 39.3 ± 9.7%. The HL of elimination (B_HL) values after either routes were similar. The terminal part of both mean pharmacokinetic curves showed a similar trend of elimination. This is the first study concerning FLU in animal species of veterinary interest. The pharmacokinetic profiles of FLU in cats were somewhat different compared to the FLU disposition in humans. Its PO F% was about 39%. This study could pave the road for the use of this active ingredient in the veterinary field. Further studies need to be undertaken to assess if this drug may be adequate in feline medicine.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
