To assess the pharmacokinetics and disposition of flupirtine (FLU) after four different formulations (intravenous [IV], oral immediate release [POIR], oral sustained release [POSR], rectal [RC]) in dogs. The Animal Welfare Committee of the University of Lublin approved the study protocol. One male and five female Labrador breed dogs were enrolled in the study. Dogs were randomly assigned to four-treatment groups, using an open, single-dose, four-period crossover design (4x4 Latin square). All dogs were fasted for 12 h overnight before each experiment. Dogs in group 1, 2 and 3 received a single dose of FLU 5mg/kg by IV, POIR and RC route, respectively. Group 4 received FLU 200 mg/dog by POSR. A 1-week wash out period was observed among the phases. Blood samples were collected at assigned times and analysed according to a previous validated HPLC method (De Vito et al. 2014). The pharmacokinetic calculations were carried out using WinNonLin v. 5.3 (Pharsight) according to a non-compartmental model. After IV administration, some adverse effects including salivation, agitation and vomiting were observed in all dogs. However, they resolved rapidly and spontaneously in about 10 min. In the other treatment groups no visible side effects were shown. The average plasma concentration vs time curves are reported in Figure. After POIR, POSR and RC administrations, FLU plasma concentrations were lower than those after IV route, but detectable over the same range of time. POIR and POSR groups showed similar Cmax and Tmax values 1549.6±916.3 and 1256.1±353.1 ng/mL, and 1.42±0.58 and 2.16±0.93 h, respectively. Their bioavailabilities (F%) were similar (41.9±8.5 and 36.8±8.4 %, respectively). RC route showed a lower value of Cmax, (635.3±266.4 ng/mL) obtained at a Tmax (2.16±0.93 h) similar to the other extravascular administrations. The RC F% was 29.4±8.8 %. The terminal part of all the mean pharmacokinetic curves showed a similar trend of elimination. CL/F values of the extravascular administrations were all not statistically different from the CL after IV injection if normalized for their own F% value. The HL of elimination time after IV route (6.20±0.88 h) showed to be shorter than those from POIR (7.4±1.9 h), POSR (7.1±0.8 h) and RC (7.7±1.9 h). Although no minimal effective plasma concentrations of FLU are reported in humans and animals so far, the 5 mg/kg FLU by POIR and POSR in dogs gave plasma concentrations similar to those obtained in humans undergoing clinical treatment. Further studies are now requested to assess if this drug may be effective in canine medicine.
PHARMACOKINETICS AND DISPOSITION OF FLUPIRTINE AFTER ADMINISTRATION OF FOUR DIFFERENT FORMULATIONS IN DOGS / DE VITO, Virginia; Lebkowska Wieruszewska, B; Shaban, A; Kowalski, Cj; Lisowski, A; 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 AND DISPOSITION OF FLUPIRTINE AFTER ADMINISTRATION OF FOUR DIFFERENT FORMULATIONS IN DOGS
DE VITO, Virginia;
2014-01-01
Abstract
To assess the pharmacokinetics and disposition of flupirtine (FLU) after four different formulations (intravenous [IV], oral immediate release [POIR], oral sustained release [POSR], rectal [RC]) in dogs. The Animal Welfare Committee of the University of Lublin approved the study protocol. One male and five female Labrador breed dogs were enrolled in the study. Dogs were randomly assigned to four-treatment groups, using an open, single-dose, four-period crossover design (4x4 Latin square). All dogs were fasted for 12 h overnight before each experiment. Dogs in group 1, 2 and 3 received a single dose of FLU 5mg/kg by IV, POIR and RC route, respectively. Group 4 received FLU 200 mg/dog by POSR. A 1-week wash out period was observed among the phases. Blood samples were collected at assigned times and analysed according to a previous validated HPLC method (De Vito et al. 2014). The pharmacokinetic calculations were carried out using WinNonLin v. 5.3 (Pharsight) according to a non-compartmental model. After IV administration, some adverse effects including salivation, agitation and vomiting were observed in all dogs. However, they resolved rapidly and spontaneously in about 10 min. In the other treatment groups no visible side effects were shown. The average plasma concentration vs time curves are reported in Figure. After POIR, POSR and RC administrations, FLU plasma concentrations were lower than those after IV route, but detectable over the same range of time. POIR and POSR groups showed similar Cmax and Tmax values 1549.6±916.3 and 1256.1±353.1 ng/mL, and 1.42±0.58 and 2.16±0.93 h, respectively. Their bioavailabilities (F%) were similar (41.9±8.5 and 36.8±8.4 %, respectively). RC route showed a lower value of Cmax, (635.3±266.4 ng/mL) obtained at a Tmax (2.16±0.93 h) similar to the other extravascular administrations. The RC F% was 29.4±8.8 %. The terminal part of all the mean pharmacokinetic curves showed a similar trend of elimination. CL/F values of the extravascular administrations were all not statistically different from the CL after IV injection if normalized for their own F% value. The HL of elimination time after IV route (6.20±0.88 h) showed to be shorter than those from POIR (7.4±1.9 h), POSR (7.1±0.8 h) and RC (7.7±1.9 h). Although no minimal effective plasma concentrations of FLU are reported in humans and animals so far, the 5 mg/kg FLU by POIR and POSR in dogs gave plasma concentrations similar to those obtained in humans undergoing clinical treatment. Further studies are now requested to assess if this drug may be effective in canine medicine.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
