322 research outputs found
Early phase pharmacokinetics but not pharmacodynamics are influenced by propofol infusion rate
Background: Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model.
Methods: Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1) . h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure.
Results: Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate.
Conclusions: This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1) . h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time
Extremely straightforward room temperature co-precipitation method to synthesize cubic KYF4:Yb/Er up-conversion nanoparticles in deionized water-ethanol solution
International audienceThrough extremely facile RT(room temperature) co-precipitation method in mixed deionized water and ethanol solution, cubic KYF 4 :10%Yb/5%Er up-conversion nanoparticles with excellent emission intensity and desirable fluorescence lifetime after annealing under 974 nm pulsed laser excitation have been successfully synthesized. The X-ray powder diffraction pattern has been refined by profile fit in order to obtain accurate lattice parameters. The mean crystallite size and microstrain have been calculated by Williamson-Hall method. Joint effect of crystallite size and microstrain on photoluminescence properties have been studied based on the obtained samples. Green-to-red ratios of the emission spectra and slopes of the emission intensity versus excitation laser power have been investigated. The fluorescence lifetimes of the present samples have also been reported. The extraordinarily facile synthesis route, in environment-friendly solvents, provides a novel proposal to remove some of the obstacles that hinder the up-conversion nanoparticles development
Simulated drug administration: An emerging tool for teaching clinical pharmacology during anesthesiology training
A thorough understanding of the dose-response relationship is required for optimizing the efficacy of anesthetics while minimizing adverse drug effects.(1) Nowadays, except for the inhaled anesthetics (for which end-tidal concentrations can be measured online), most of the drugs used in clinical anesthesia are administered using standard dosing guidelines, without giving due consideration to their pharmacokinetics and dynamics in guiding their administration. Various studies have found that introducing pharmacokinetics and pharmacodynamics as part of the inputs in clinical anesthesiology could lead to better patient care.(2) With this in mind, it is extremely important that clinicians understand and apply the principles of clinical pharmacology that determine the time course of a drug's disposition and effect.
Clinical pharmacology is one of the most challenging topics to teach in anesthesiology. The development of simulators to illustrate the time course of a drug's disposition and effect provides online visualization of pharmacokinetic pharmacodynamic information during the clinical use of anesthetics. The aim of this review is to discuss the importance of simulation as a clinical pharmacology teaching tool for trainees in anesthesiology
Influence of steep Trendelenburg position and CO2 pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy
The steep (40 degrees) Trendelenburg position optimizes surgical exposure during robotic prostatectomy. The goal of the current study was to investigate the combined effect of this position and CO2 pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during these procedures.
Physiological data were recorded during the whole surgical procedure in 31 consecutive patients who underwent robotic endoscopic radical prostatectomy under general anaesthesia. Heart rate, mean arterial pressure, central venous pressure, Sp(o2), Pe'(co2), P-Plat, tidal volume, compliance, and minute ventilation were monitored and recorded. Arterial samples were obtained to determine the arterial-to-end-tidal CO2 tension gradient. Continuous regional cerebral tissue oxygen saturation (Sct(o2)) was determined by near-infrared spectroscopy.
Although patients were in the Trendelenburg position, all variables investigated remained within a clinically acceptable range. Cerebral perfusion pressure (CPP) decreased from 77 mm Hg at baseline to 71 mm Hg (P=0.07), and Sct(o2) increased from 70% to 73% (P < 0.001). Pe'(co2) increased from 4.12 to 4.79 kPa (P < 0.001) and the arterial-to-Pe'(co2) tension difference increased from 1.06 kPa in the normal position to a maximum of 1.41 kPa (P < 0.001) after 2 h in the Trendelenburg position.
The combination of the prolonged steep Trendelenburg position and CO2 pneumoperitoneum was well tolerated. Haemodynamic and pulmonary variables remained within safe limits. Regional cerebral oxygenation was well preserved and CPP remained within the limits between which cerebral blood flow is usually considered to be maintained by cerebral autoregulation
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