Pharmacokinetic and pharmacodynamic evaluation of propofol administered to cats in a novel, aqueous, nano‐droplet formulation or as an oil‐in‐water macroemulsion¹

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.

Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats

“…The clearance of propofol in cats undergoing ketofol infusion was quite slow (692.36 ± 326.18 mL/h/kg) and lower than that reported in cats after single IV bolus (Cl B 1032 mL/h/kg; Cleale et al. , 2009) and in other species after propofol and ketamine infusion (Nolan & Reid, 1993; Correia et al.…”

“…However, the sampling time in our study and the reported studies in sheep and dogs was 24 h after the end of the infusion, whereas the infusion time was shorter in cats than in the other mentioned species (<30 min vs. 60 min). After a single IV bolus of propofol in cats, an elimination half‐life of 8.7 h was reported (Cleale et al. , 2009).…”

“…Hanna et al. (1988) reported a Cl B of about 1278 mL/h/kg for ketamine after a single IV dose of 25 mg/kg, whereas Cleale et al. (2009) reported a Cl B of 1032 mL/h/kg after a single IV bolus of propofol (7 mg/kg).…”

“…, 1988) and propofol (Adam et al. , 1980; Cleale et al. , 2009) in cats have been investigated as single IV bolus administration, but no pharmacokinetic data are available regarding infusion of the combination of the two drugs.…”

Respostas cardiorrespiratória e metabólica do propofol nas formulações em emulsão lipídica ou microemulsão em gatas

“…Entre grupos, a PaCO 2 do EMU foi maior de T15 até T90 em relação ao MICRO. A diferença apresentada pode ser atribuída à formulação do propofol em microemulsão, frente ao metabolismo diferenciado dos gatos, uma vez que esse episódio não ocorreu em estudo de CORRÊA et al (2010), utilizando a mesma formulação em cães, bem como em outros estudos, utilizando diferentes formulações de propofol em cães (MOREY et al, 2006) e gatos (CLEALE et al, 2009).…”