Portal de Pesquisa da BVS Veterinária

Tese em Português | VETTESES | ID: vtt-1964

Resumo

Os felinos sao deficientes na biotransformacao do propofol e os dados em relacao a farmacocinetica nesta especie sao escassos. Alem do mais, alteracoes nas formulacoes dos farmacos podem acarretar variacoes farmacocineticas. O objetivo deste estudo foi determinar o perfil farmacocinetico do propofol em gatos e comparar as formulacoes em emulsao lipidica e em nanoemulsao apos infusao continua. Utilizaram-se seis gatos higidos, castrados, com peso medio de 4,21 ?} 0,81 kg, em um estudo randomizado e autocontrole. Os animais receberam 10 mg/kg de propofol a 1% em emulsao lipidica (EMU) ou em nanoemulsao (NANO) durante 30 segundos e imediatamente apos, iniciou se a infusao de 0,3 mg/kg/min da mesma formulacao durante 60 minutos. Apos 30 dias receberam o mesmo tratamento com a formulacao oposta. Amostras de 3 ml de sangue venoso foram colhidas por meio de um cateter venoso central inserido na veia jugular nos tempos 0 (basal), 2, 5, 10, 15, 30 e 60 minutos de infusao e aos 5, 10, 15, 30, 60 e 90 minutos e 2, 3, 4, 6, 10 e 24 horas apos o final da infusao. As concentracoes plasmaticas e um estudo de bioequivalencia foram analisados em laboratorio especializado levando se em consideracao os valores logaritmicos de concentracao maxima (Cmax) e area sob a curva do final da infusao a ultima amostra (ASC1-25). Os parametros farmacocineticos de Volumes de distribuicao (Vd), meias vidas de distribuicao (t1/2 ?¿) e de eliminacao (t1/2?À e t1/2?Á), clearances (Cl central e compartimentais) e microconstantes (k10, k12, k21, k13 e k31) foram determinados com auxilio computacional e tabelas de conversao a partir da curva de decaimento da concentracao plasmatica versus tempo ao final da infusao. Nao houve diferenca entre as formulacoes em relacao a todos os parametros, entretanto nao foi observada bioequivalencia entre as formulacoes devido a ASC1-25 estar fora dos intervalos de confianca, porem, o numero de animais foi baixo para os padroes de bioequivalencia. Os valores de t1/2 ?¿, ?À e ?Á foram de 10,2?}8,4 minutos e 1,34?} 0,25 e 21,52?}10,33 horas para a nanoemulsao e de 11,4?}5,4 minutos e 1,25?}0,45 e 17,92?}7,83 horas para a emulsao lipidica. Os volumes de distribuicao foram altos com V3 e Vdss de 18,63?}10,98 e 23,23?}12,30 litros/kg para a nanoemulsao e de 13,14?}6,56 e 18,12?}8,54 litros/kg para a emulsao lipidica. Os Cl foram baixos com um Cl central de 22,20?}10,83 ml/kg/min para a nanoemulsao e de 23,42?}13,50 ml/kg/min para emulsao lipidica. Conclui se que a farmacocinetica do propofol em gatos apos infusao continua difere das demais especies caracterizando se por uma grande distribuicao tecidual e uma lenta eliminacao. A formulacao em nanoemulsao apresenta caracteristicas farmacocineticas semelhantes as da emulsao lipidica

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Cats are deficient in the metabolism of propofol and the data on the pharmacokinetics in this species are scarce. Besides, but changes in the formulations of drugs may cause pharmacokinetic variations. The aim this study was to determine the pharmacokinetic profile of propofol in cats and compare the lipid emulsion formulations and nanoemulsion after continuous infusion. We used six healthy cats, weight 4.21 Â 0.81 kg in a randomized and self control. The animals received 10mg/kg of propofol 1% in the lipid emulsion or nanoemulsion for 30 seconds and immediately after infusion was started 0.3 mg / kg / min of the same formulation for 60 minutes. After 30 days received the same treatment with the formulation opposite.Samples of 3 ml of venous blood were collected via a central venous catheter inserted in the jugular vein at 0 (baseline), 2, 5, 10, 15, 30 and 60 minutes of infusion and at 5, 10, 15, 30, 60 and 90 minutes and 2, 3, 4, 6, 10 and 24 hours after the end of the infusion. Plasma concentrations and a bioequivalence study in specialized laboratory were analyzed taking into account the logarithmic values of maximum concentration (Cmax) and area under the curve of the end of infusion to the last sample (AUC1-25). The pharmacokinetic parameters of volume of distribution (Vd), distribution half-lives (t1/2α) and elimination (t1/2β and t1/2γ), clearances (Cl central and compartmental) and microconstantes (k10, k12, k21, k13 and k31) were determined using computational and conversion tables from the decay curve of plasma concentration versus time at the end of the infusion. There was no difference between the formulations with respect to all parameters, however there was no bioequivalence between formulations AUC1-25 due to being outside the confidence intervals, however, the number of animals was low by the standards of bioequivalence. The values of t1/2α, β and γ were 10,2Â8,4 minutes and 1.34 Â 0.25 and 21.52 Â 10.33 hours for the nanoemulsion and 11,4Â5,4 minutes and 1.25 Â 0.45 and 17.92 Â 7.83 hours for the lipid emulsion. The volumes of distribution were high with V3 and Vdss of 18,63Â10,98 and 23,23Â12,30 liters/kg for the nanoemulsion and 13,14Â6,56 and 18,12Â8,54 liters/kg for lipid emulsion. The Cl were low with a Cl central to 22,20Â10,83 ml/kg/min for the nanoemulsion and 23,42Â13,50 ml/kg/min for lipid emulsion. Concluded that the pharmacokinetics of propofol in cats after continuous infusion differs from other species characterized by a wide tissue distribution and slow elimination. The nanoemulsion formulation has similar pharmacokinetic characteristics of the lipid emulsion

Biblioteca responsável: BR68.1