Pharmacokinetics of propofol nanoemulsion in dogs/Farmacocinetica do propofol em nanoemulsao em caes

Propofol nanoemulsion is a new formulation consisting of nanoemulsified systems, characterized by the absence of lipid vehicle. Changes in drug vehicle may alter the pharmacokinetics and result in different distribution and elimination rates ofpropofol. The aim of this study was to evaluate the pharmacokinetics of a new oil in water propofol nanoemulsion formulation, compared to the traditional lipid emulsion. Six neutered female mixed-breed dogs were used (10.7 ± 1.5kg) in a randomized and self control trial with 30 days interval. They received both propofol formulations administered as a bolus dose of 8mg [kg.sup.-1] followed by 60 minutes continuous infusion at 0.4mg [kg.sup.-1] [min.sup.-1] rate. Arterial blood samples were collected just before induction (0), 2, 5, 10, 15, 30, and 60 minutes after the bolus dose, and after the end of the infusion at five, 10, 15, 30, 60, and 90 minutes and 2, 3, 4, 6, 10, and 24 hours. There were no significant differences in the evaluated pharmacokinetics parameters that included volume of distribution, clearance, elimination rate constant, half-life, and distribution constants, demonstrating that propofol nanoemulsion has no pharmacokinetics differences when compared to the traditional formulation. Key words: propofol, pharmacokinetics, dogs, nanoemulsion. O propofol em nanoemulsao e uma nova formulacao constituida por sistemas nanoemulsionados, caracterizado pela ausencia do veiculo lipidico. A modificacao do veiculo pode acarretar alteracoes farmacocineticas, resultando em diferentes taxas de distribuicao e excrecao do propofol. O objetivo deste estudo foi avaliar a farmacocinetica de uma nova formulacao de propofol em nanoemulsao do tipo oleo em agua, comparando com a formulacao tradicional em emulsao lipidica. Foram utilizadas seis cadelas sem raca definida, castradas (10,7 ± 1,5kg), em estudo aleatorio e de autocontrole, que receberam as duas formulacoes de propofol com intervalo de 30 dias entre os tratamentos, sendo administrada uma dose bolus de 8mg [kg.sup.-1], seguida de infusao continua por 60 minutos na taxa de 0,4mg [kg.sup.-1] [min.sup.-1]. Amostras de sangue arterial foram colhidas momentos antes da inducao (0), 2, 5, 10, 15, 30 e 60 minutos apos a dose bolus e apos o termino da infusao nos tempos 5, 10, 15, 30, 60 e 90 minutos e 2, 3, 4, 6, 10 e 24 horas. Nao foram encontradas diferencas significativas entre os parametros farmacocineticos de volume de distribuicao, clearance, constante de eliminacao,