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Pharmacokinetic and pharmacodynamic evaluation of propofol administered to cats in a novel, aqueous, nano-droplet formulation or as an oil-in-water macroemulsion.
Cleale, R M; Muir, W W; Waselau, A-C; Lehmann, M W; Amodie, D M; Lerche, P.
Afiliação
  • Cleale RM; Fort Dodge Animal Health, PO Box 5366, Princeton, NJ 08543-5366, USA. clealer@pt.fdah.com
J Vet Pharmacol Ther ; 32(5): 436-45, 2009 Oct.
Article em En | MEDLINE | ID: mdl-19754909
ABSTRACT
This study evaluated pharmacokinetic and pharmacologic properties of a novel, non-lipid microemulsion, 1% w/v formulation of propofol to a conventional macroemulsion formulation of propofol (Rapinovet) in cats. The study utilized a two-period crossover design with two treatments and 10 female, intact, purpose bred domestic shorthair cats. Cats were fitted with telemetry transmitters for direct measurement of arterial blood pressure, pulse rate, electrocardiogram (ECG, lead II), and body temperature. At least 7 days separated treatments. Orotracheal intubation was the clinical endpoint utilized to evaluate adequate depth of anesthesia. Blood samples were drawn from jugular vascular access ports before propofol treatment; 3, 5, 15, 25, 35, 45, and 60 min and then 2, 3, 6, 8, 12, 18, and 24 h after administration of propofol into a cephalic vein. Whole blood samples were assayed for propofol concentrations using a gas chromatography/mass spectrometry method validated for feline blood at a limit of quantification of 5 ng/mL. Pulse rate, ECG, heart rhythm, respiratory rate, systolic, diastolic and mean arterial blood pressures, SpO2, and body temperature were monitored continuously during each anesthetic episode. Time to lateral recumbency, orotracheal intubation, and extubation, time to sternal recumbency during recovery, times to adverse events, and doses of propofol required for induction to anesthesia were documented. Cats required 6.96 +/- 0.90 mg propofol/kg from the novel microemulsion formulation of propofol and 7.07 +/- 1.55 mg propofol/kg from Rapinovet to achieve anesthesia adequate to allow orotracheal intubation (P > 0.05). Areas under the dose-normalized propofol concentration by time curves (AUC(0-LOQ)) and maximum propofol concentrations (C(max)) were equal for the novel microemulsion formulation of propofol and Rapinovet (P > 0.05). Effects of anesthesia induction doses on cardiorespiratory values were comparable between treatments, and consistent with known effects of propofol anesthesia. Results provide evidence that the novel microemulsion formulation of propofol and Rapinovet macroemulsion produced comparable pharmacodynamic, physiological, and pharmacokinetic responses in cats. The unique composition of the microemulsion formulation, and the presence of an antimicrobial preservative minimize the potential for bacterial contamination and prolong shelf life.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Propofol / Anestésicos Intravenosos Limite: Animals Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Propofol / Anestésicos Intravenosos Limite: Animals Idioma: En Ano de publicação: 2009 Tipo de documento: Article