Assuntos
Dexmedetomidina/farmacocinética , Hipnóticos e Sedativos/farmacocinética , Animais , Gatos/metabolismo , Dexmedetomidina/administração & dosagem , Dexmedetomidina/sangue , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/sangue , Infusões Intravenosas/veterinária , Modelos BiológicosRESUMO
This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.
Assuntos
Analgésicos não Narcóticos/farmacocinética , Anestésicos Inalatórios/farmacocinética , Gatos/metabolismo , Dexmedetomidina/farmacocinética , Isoflurano/farmacocinética , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/sangue , Anestesia por Inalação/veterinária , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/sangue , Animais , Dexmedetomidina/administração & dosagem , Dexmedetomidina/sangue , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Isoflurano/administração & dosagem , Isoflurano/sangue , Alvéolos PulmonaresRESUMO
This study examined the effect of amantadine, an N-methyl-d-aspartate receptor antagonist, on the thermal antinociceptive effect of oxymorphone in cats. Six adult healthy cats were used. After baseline thermal threshold determinations, oxymorphone was administered intravenously to maintain plasma oxymorphone concentrations of 10, 20, 50, 100, 200, and 400 ng/mL. In addition, amantadine, or an equivalent volume of saline, was administered intravenously to maintain a plasma amantadine concentration of 1100 ng/mL. Thermal threshold and plasma oxymorphone and amantadine concentrations were determined at each target plasma oxymorphone concentration. Effect maximum models were fitted to the oxymorphone concentration-thermal threshold data, after transformation in % maximum response. Oxymorphone increased skin temperature, thermal threshold, and thermal excursion (i.e., the difference between thermal threshold and skin temperature) in a concentration-dependent manner. No significant difference was found between the amantadine and saline treatments. Mean ± SE oxymorphone EC(50) were 14.2 ± 1.2 and 24.2 ± 7.4 ng/mL in the amantadine and saline groups, respectively. These values were not significantly different. Large differences in oxymorphone EC(50) in the saline and amantadine treatment groups were observed in two cats. These results suggest that amantadine may decrease the antinociceptive dose of oxymorphone in some, but not all, cats.
Assuntos
Amantadina/farmacologia , Analgésicos não Narcóticos/farmacologia , Analgésicos Opioides/farmacologia , Temperatura Alta/efeitos adversos , Oximorfona/farmacologia , Dor/tratamento farmacológico , Amantadina/administração & dosagem , Amantadina/farmacocinética , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/farmacocinética , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Animais , Gatos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Oximorfona/administração & dosagem , Oximorfona/farmacocinéticaRESUMO
This study reports the pharmacokinetics of oxymorphone in spayed female cats after intravenous administration. Six healthy adult domestic shorthair spayed female cats were used. Oxymorphone (0.1 mg/kg) was administered intravenously as a bolus. Blood samples were collected immediately prior to oxymorphone administration and at various times up to 480 min following administration. Plasma oxymorphone concentrations were determined by liquid chromatography-mass spectrometry, and plasma oxymorphone concentration-time data were fitted to compartmental models. A three-compartment model, with input in and elimination from the central compartment, best described the disposition of oxymorphone following intravenous administration. The apparent volume of distribution of the central compartment and apparent volume of distribution at steady state [mean ± SEM (range)] and the clearance and terminal half-life [harmonic mean ± jackknife pseudo-SD (range)] were 1.1 ± 0.2 (0.4-1.7) L/kg, 2.5 ± 0.4 (2.4-4.4) L/kg, 26 ± 7 (18-38) mL/min.kg, and 96 ± 49 (62-277) min, respectively. The disposition of oxymorphone in cats is characterized by a moderate volume of distribution and a short terminal half-life.
Assuntos
Analgésicos Opioides/farmacocinética , Gatos/sangue , Oximorfona/farmacocinética , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Animais , Cromatografia Líquida/veterinária , Feminino , Meia-Vida , Injeções Intravenosas/veterinária , Análise dos Mínimos Quadrados , Modelos Lineares , Taxa de Depuração Metabólica , Oximorfona/administração & dosagem , Oximorfona/sangue , Espectrometria de Massas em Tandem/veterináriaRESUMO
This study reports the pharmacokinetics of amantadine in cats, after both i.v. and oral administration. Six healthy adult domestic shorthair female cats were used. Amantadine HCl (5 mg/kg, equivalent to 4 mg/kg amantadine base) was administered either intravenously or orally in a crossover randomized design. Blood samples were collected immediately prior to amantadine administration, and at various times up to 1440 min following intravenous, or up to 2880 min following oral administration. Plasma amantadine concentrations were determined by liquid chromatography-mass spectrometry, and plasma amantadine concentration-time data were fitted to compartmental models. A two-compartment model with elimination from the central compartment best described the disposition of amantadine administered intravenously in cats, and a one-compartment model best described the disposition of oral amantadine in cats. After i.v. administration, the apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state [mean ± SEM (range)], and the clearance and terminal half-life [harmonic mean ± jackknife pseudo-SD (range)] were 1.5 ± 0.3 (0.7-2.5) L/kg, 4.3 ± 0.2 (3.7-5.0) L/kg, 8.2 ± 2.1 (5.9-11.4) mL·min/kg, and 348 ± 49 (307-465) min, respectively. Systemic availability [mean ± SEM (range)] and terminal half-life after oral administration [harmonic mean ± jackknife pseudo-SD (range)] were 130 ± 11 (86-160)% and 324 ± 41 (277-381) min, respectively.