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Study Of Pharmacodynamics And Pharmacokinetics Of Propofol Anaesthesia By Constant Speed Administration Intravenously On Dogs

Posted on:2008-11-24Degree:MasterType:Thesis
Country:ChinaCandidate:L Y PengFull Text:PDF
GTID:2143360218453780Subject:Clinical Veterinary Medicine
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The anaesthetic effects and pharmacokinetics of propofol by constant speed administrationwere investigated, and the optimum anaesthetic dose of propofol was selected on small dogs inthis study.Dogs were performed induction of anaesthesia with different dose (2.5-6 mg/kg) of propofolintravenously (Ⅳ). Heart rate (HR), respiratory rate (RR), pulse oxygen saturation (SPO2), bodytemperature (T), mean arterial pressure (MAP), analgesia, sedative, and muscle relaxation weremeasured after the beginning of the propofol infusion. Statistical analysis was performed using anANOVA. The results indicated that 4 mg/kg of propofol could produce good induction effect ofanesthesia on small dogs.The pharmacokinetics of propofol in dogs were investigated. Dogs were performed inductionof anesthesia with 4 mg/kg of propofol intravenously (Ⅳ) by the microinfsion pump over 90seconds, and plasma was collected and anticoagulated with heparin at 2, 5, 8, 11,14, 20, 30, 45, 60and 90 minutes after the beginning of the propofol infusion respectively. Plasma protein wasprecipitated and following extracted with acetonitrile for the extraction of propofol. The extractiveof propofol was redissolved in high-performance liquid chromatograph (HPLC) mobil phase andwas detected by the combination of HPLC and fluorescence detection. The results indicated thatthe procedure was more rapid, simpler, sensitive and accurate, which could satisfy the monitoringrequirement of propofol concentration in plasma. The data were analyzed with the MCPKPsoftware. Concentration-time data were fitted to a two-compartment open pharmacokinetic model,which has been identified as the appropriate model for pharmacokinetic analysis of propofoldisposition in dogs. The pharrnacokinetic parameter as following, distribution half-life (T1/2α) was4-11 min, elimination half-life (T1/2β) was about 28 min, body learance (ClB) was 5-6 L/kg/h,elimination rate constant (Kel) was 4.36±1.15h, and apparent volume of distribution (Vd) was3.31±1.14L/kg. The result indicates that propofol was distributed rapidly and eliminated slowly indogs. The rapid distribution of propofol resulted in rapidly descend of the drug concentration inplasma, which is the reason of fast recovery.In addition, in order to check the clinical anesthetic effect, several different infusion rates ofpropofol were designed in dogs. The results showed that dogs appeared respiratory depression, HRincrease, SPO2 serious decreas, and involuntary movement of limbs after infusion with 5mg/(kg·min) of propofol for maintenance anesthesia. However, the dogs showed smooth anduneventful anaesthesia, sTab. respiration, and light SPO2 descent after infusion with 0.3-0.4mg/(kg·min) of propofol, which indicated the dose scope of propofol is fit to maintenance of anesthesia on dogs. Consequently, 0.3 mg/(kg·min), 0.35 mg/(kg·min) and 0.4 mg/(kg·min) ofpropofol were selected to performe maintenance of anesthesia on dogs. HR, RR, SPO2, T, MAP,effect of analgesia, effect of sedative, and effect of muscle relaxation were measured after thebeginning of the propofol infusion. Statistical analysis was performed using an ANOVA, Theresults showed that dogs, administered 0.4 mg/(kg·min) of propofol, presented satisfactory effect ofsedative, better effect of analgesia and muscle relaxation, light RR increase, SPO2 keeped about90%, which can not affect normal physiological function of dogs, HR increase, MAP increase, andnormal electrocardiographic wave. The results indicated that induction of anesthesia with 4 mg/kgof propofol and maintenance of anesthesia with 0.4 mg/(kg·min) of propofol could produced goodanaesthetic effect.When dogs was performed induction of anesthesia with 4 mg/kg of propofol and maintenanceof anesthesia with 0.4 mg/(kg·min) of propofol, the different time plasma drug concentration ofpropofol was monitored by HPLC- fluorescence detection after the beginning of the propofolinfusion. The study provided some based data for clinical application of propofol on small dogs.
Keywords/Search Tags:propofol, constant speed administration intravenously, anaesthetic effect, Pharmacokinetics
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