title: Evidence of Different Propofol Pharmacokinetics under Short and Prolonged Infusion Times in Rabbits.
abstract: Propofol is an anaesthetic widely used in both human beings and animals. However, the characterization of propofol pharmacokinetics (PK) is not well understood when long-term infusions are used. The main objective of this study was to explore the PK behaviour of propofol in a rabbit model during short and prolonged propofol infusions and to develop an internally validated PK model, for propofol dose individualization in the rabbit for future use. Population 1 (P1) was constituted by seven New Zealand rabbits and was used to characterize the PK profile of propofol at short infusions. Animals were anaesthetized with a bolus of 20 mg/kg, followed by an infusion rate of 50 mg/kg/hr of propofol at 1%, which was then maintained for 30 min. A second rabbit population (P2, n = 7) was sedated according to reflexes responses and Index of Consciousness values, for 20 consecutive hours using propofol 2% aiming at characterizing propofol behaviour at long-term infusions. Clinical data and blood samples were collected at specific time-points in both populations. Propofol plasma concentrations were determined by gas chromatography/ion trap mass spectrometry. The NONMEM VII software was used to evaluate the relationships between dose and plasma concentrations. A linear two-compartment model with different central compartment volume and plasma clearance (separately modelled in the two populations) was the one that best described propofol concentrations. The time course of propofol plasma concentrations was well characterized by the PK model developed, which simultaneously accounts for propofol short- and long-term infusions and can be used to optimize future PK studies in rabbits.
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department of the University of Trás-os-Montes and Alto Douro (UTAD), Portugal.|Laboratory Animal Science Institute of Molecular and Cell Biology (IBMC), Porto University, Porto, Portugal.|UCIBIO@REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Campos
authors.affiliation: IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologia da Saúde, CESPU, Paredes, Portugal.|Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Monteiro
authors.affiliation: Platform of Oncology, Hospital Quirón Torrevieja, Torrevieja, Alicante, Spain.|Cathedra of Multidisciplinary Oncology - UCAM, Catholic University of San Antonio, Murcia, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Valenzuela
authors.affiliation: Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Gonçalinho
authors.affiliation: UCIBIO@REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Paula Guedes
authors.initials: PG
authors.lastname: de Pinho
authors.affiliation: Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Fresco
authors.affiliation: Laboratory Animal Science Institute of Molecular and Cell Biology (IBMC), Porto University, Porto, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Félix
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department of the University of Trás-os-Montes and Alto Douro (UTAD), Portugal.|Laboratory Animal Science Institute of Molecular and Cell Biology (IBMC), Porto University, Porto, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Antunes
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol