Pharmacodynamic principles and target concentration intervention

This tutorial reviews the principles of dose individualisation with an emphasis on target concentration intervention (TCI). Once a target effect is chosen then pharmacodynamics can predict the target concentration and pharmacokinetics can predict the target dose to achieve the required response. Dose individualisation can be considered at three levels: population, group and individual. Population dosing, also known as fixed dosing or “one size fits all” is often used but is poor clinical pharmacology; group dosing uses patient features such as weight, organ function and co-medication to adjust the dose for a typical patient; individual dosing uses observations of patient response to inform about pharmacokinetic and pharmacodynamics in the individual and use these individual differences to individualise dose.

Median effective plasma target concentration of propofol administered for lumbar surgery during inhala-tion-intravenous balanced anesthesia when BIS is 50 / 临床麻醉学杂志

Objective To investigate the median effective plasma target concentration of propo-fol (Cp50 )needed for lumbar surgery during inhalation-intravenous balanced anesthesia when BIS is 50.Methods Patients aged 40-56 years,scheduled for vertebral pulp ectomy were included.Anesthe-sia were maintained by TCI of propofol,sevoflurane 0.5 MAC,remifentanyl 0.2 μg·kg-1 ·min-1 , and vecuronium 0.08 mg·kg-1 ·h-1 .The target plasma concentration of propofol was initially set at 1.8 μg/ml,and adjusted by the sequential up-and-down methods,based on BIS index.The Cp50 of propofol and its 95% confidence interval (CI)were calculated.Results Twenty-six patients were en-rolled in this study.The median effective plasma target concentration of propofol was 1.61 μg/ml (95%CI 1.52-1.70)μg/ml.Conclusion The Cp50 of propofol needed for maintaining the BIS index of 50 is 1.61 μg/ml during the anesthesia with 0.5 MAC of sevoflurane combined with remifentanyl in lumbar surgery.

Clinical observation of propofol compound remifentailuesed for painless abortions surger / 中国药学杂志

OBJECTIVE: To compare the efficacies of different target concentrations of propofol combinded with remifentanil for painless induced abortions, thus to explore the best target concentrations. METHODS: One hundred and twenty ASAI-II patients receiving elective painless induced abortions between May 2011 and October 2011 were randomly divided into three groups. The target concentrations of propofol were 2, 3, and 4 μg·mL-1, respectively. The hemodynamic changes and body movements at different time and the time of leaving operating room in the three groups were compared. RESULTS: The patients in the three groups all finished operations. The MAPs and HRs when dilating uterine and aspirating embryo bud were significantly increased, and the incidence of body movements was the highest in the 2 μg·mL-1 group; the number of apnea cases and the time of leaving operation room in the 4 μg·mL-1 group were significantly higher than the other two groups. CONCLUSION: When using propofol at target concentration of 3 μg·mL-1 combined with remifentanil at target concentration of 3 μg·mL-1 for painless induced abortions, the patients had stable perioperative MAP and HR, less apnea cases, and shorter time of leaving operation room. So these are the ideal target plasma concentrations for controlled anesthesia for painless induced abortions.

Overviews and advances in studies of target concentration intervention / 中国药学杂志

OBJECTIVE: To review the target concentration intervention (TCI) theory and provide reliable evidences for the optimization of drug treatment in clinical practice. METHODS: Relevant literatures were extensively and comprehensively reviewed. RESULTS: Since 1960s, therapeutic drug monitoring (TDM) had been applied in clinical practice to realize individualized drug administration. Due to some potential limitations of TDM such as neglecting inter-individual variability and failure to take drug effects into account, more and more scholars proposed a new theory which is called TCI as an alternative of TDM. The TCI approach takes advantage of known patient variables, pharmacokinetics and pharmacodynamics to interpret drug effect and concentration observations. It not only overcomes the defects of TDM, but also provides a complete strategy for individual administration. CONCLUSION: TCI is an extension of TDM, which has clinical significance for individualized therapy.