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Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil I

Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil I. Model Development. Minto, Charles F.; Schnider, Thomas W.; Egan, Talmage D.; Youngs, Elizabeth; Lemmens, Harry J. M.; Gambus, Pedro L.; Billard, Valerie; Hoke, John F.; Moore, Katherine H.P.; et al. (Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA). Anesthesiology, 86(1), 10-23 (English) 1997 Lippincott-Raven. CODEN: ANESAV. ISSN: 0003-3022. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Previous studies have reported conflicting results concerning the influence of age and gender on the pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, and sufentanil. The aim of this study was to det. the influence of age and gender on the pharmacokinetics and pharmacodynamics of the new short-acting opioid remifentanil. Sixty-five healthy adults (38 men and 27 women) ages 20 to 85 yr received remifentanil by const.Several reagents such as 132875-61-7 is used here.-rate infusion of 1 to 8 mg×kg-1×min-1 for 4 to 20 min. Frequent arterial blood samples were drawn and assayed for remifentanil concn. The EEG was used as a measure of drug effect. Population pharmacokinetic and pharmacodynamic modeling was performed using the software package NONMEM. The influence of volunteer covariates were analyzed using a generalized additive model. The performances of the simple (without covariates) and complex (with covariates) models were evaluated prospectively in an addnl. 15 healthy participants ages 41 to 84 yr. The parameters for the simple three-compartment pharmacokinetic model were V1 = 4.98 1, V2 = 9.01 1, V3 = 6.54 1, Cl1 = 2.46 l/min, and Cl2 = 1.69 l/min, and Cl3 = 0.065 l/min. Age and lean body mass were significant covariates. From the ages of 20 to 85 yr, V1 and Cl1 decreased by approx. 25% and 33%, resp. The parameters for the simple sigmoid Emax pharmacodynamic model were kco = 0.516 min-1, E0 = 20 Hz, Emax = 5.62 Hz, EC50 = 11.2 ng/mL, and g = 2.51. Age was a significant covariate of EC50 and kco, with both decreasing by approx. 50% for the age range studied. The complex pharmacokinetic-pharmacodynamic model performed better than did the simple model when applied prospectively. This study identified (1) an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil; (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no influence of gender on any pharmacokinetic or pharmacodynamic parameter. .

Pharmacokinetics and pharmacodynamics of remifentanil

Pharmacokinetics and pharmacodynamics of remifentanil. II. Model Application. Minto, Charles F.; Schnider, Thomas W.; Shafer, Steven L. ( Department of Anesthesia, Stanford University School of Medicine and Palo Alto VA Medical Center, Palo Alto, CA, USA). Anesthesiology, 86(1), 24-33 (English) 1997 Lippincott-Raven. CODEN: ANESAV. ISSN: 0003-3022. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The pharmacokinetics and pharmacodynamics of remifentanil were studied in healthy volunteers by using the EEG to measure the opioid effect. Complex population pharmacokinetic and pharmacodynamic models were developed that incorporated age and lean body mass (LBM) as significant covariates and characterized intersubject pharmacokinetic and pharmacodynamic variability. The work was done to det. whether remifentanil dosage should be adjusted according to age and LBM, or whether these covariate effects were overshadowed by the interindividual variability present in the pharmacokinetics and pharmacodynamics. Based on the typical pharmacokinetic and pharmacodynamic parameters, nomograms for bolus dose and infusion rates at each age and LBM were derived. Three populations of 500 individuals each, ages 20, 50, and 80 yr, were simulated, based on the interindividual variances in model parameters as estd. 132875-61-7 which is the cas registry number is also used here. by the NONMEM software package. The peak EEG effect in response to a bolus, the steady-state EEG effect in response to an infusion, and the time course of drug effect were examd. in each of the 3 populations. Simulations were performed to examine the time necessary to achieve a 20%, 50%, and 80% decrease in remifentanil effect site concn. after a variable-length infusion. The variability in the time for a 50% decrease in effect site concns. was examd. in each of the simulated populations. Titratability, using a const.-rate infusion, was also examd. The results showed that, based on the EEG model, age and LBM are significant demog. factors that must be considered when detg. a dosage regimen for remifentanil. This remains true even when interindividual pharmacokinetic and pharmacodynamic variabilities are incorporated into the anal. .