Pharmacokinetics and pharmacodynamics of propofol in patients undergoing abdominal aortic surgery.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 1
Abstract
Available propofol pharmacokinetic protocols for target-controlled infusion (TCI) were obtained from healthy individuals. However, the disposition as well as the response to a given drug may be altered in clinical conditions. The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol during total intravenous anesthesia (propofol/fentanyl) monitored by bispectral index (BIS) in patients scheduled for abdominal aortic surgery. Population nonlinear mixed-effect modeling was done with Nonmem. Data were obtained from ten male patients. The TCI system (Diprifusor) was used to administer propofol. The BIS index served to monitor the depth of anesthesia. The propofol dosing was adjusted to keep BIS level between 40 and 60. A two-compartment model was used to describe propofol PK. The typical values of the central and peripheral volume of distribution, and the metabolic and inter-compartmental clearance were V(C) = 24.7 l, V(T) = 112 l, Cl = 2.64 l/min and Q = 0.989 l/min. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment with the rate constant for the distribution to the effector compartment equal to 0.240 min(-1). The BIS index was linked to the effect site concentrations through a sigmoidal E(max) model with EC(50) = 2.19 mg/l. The body weight, age, blood pressure and gender were not identified as statistically significant covariates for all PK/PD parameters. The population PK/PD model was successfully developed to describe the time course and variability of propofol concentration and BIS index in patients undergoing surgery.
Authors and Affiliations
Paweł Wiczling, Agnieszka Bienert, Roma Hartmann-Sobczyńska, Krzysztof Bieda, Aleksandra Marcinkowska, Maria Malatyńska, Roman Kaliszan, Edmund Grześkowiak
Keywords
Related Articles
- EP ID EP108712
- DOI -
- Views 100
- Downloads 0
Anxiolytic-like activity of zinc in rodent tests.
Because zinc deficiency induces depression and anxiety-like behavior in rodents, we examined the effects of zinc administration in several tests by measuring anxiolytic activity in mice and rats. We now report that zinc...
Melatonin-induced augmentation of collagen deposition in cultures of fibroblasts and myofibroblasts is blocked by luzindole - a melatonin membrane receptors inhibitor.
Background: Melatonin has been proven to have a regulatory influence on collagen accumulation in different types of wound. It was found to inhibit collagen accumulation in the superficial wound model but increase it in t...
Paradoxical effects of adenosine receptor ligands on hydroxyl radical generation by L-DOPA in the rat striatum.
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with selective loss of dopaminergic neurons in substantia nigra pars compacta. Among the proposed mechanisms of dopaminergic degeneration, o...
Epigallocatechin gallate accelerates healing of indomethacin-induced stomach ulcers in mice.
Management of the gastric toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) remains a crucial problem because the commercially available drugs have side effects and are often expensive. Therefore, we examined th...
Analgesic and anticonvulsant activity of new derivatives of 2-substituted 4-hydroxybutanamides in mice.
Earlier in vitro studies of the compounds marked as GT27, GT28, GT29 and BM128 revealed their inhibitory action towards murine γ-aminobutyric acid (GABA) transporters (mGAT1-mGAT4). In the present paper, the pharmacologi...