Two structural models were considered for M1-cis d the second of the two models had a provision for conversion of rolofylline to M1-cis, while c the first did not. The model parameters which influenced the pharmacokinetics of both rolofylline and M1-trans were held fixed to the optimal parameterization of round 2, and parameters which influenced the pharmacokinetics of M1-cis were optimized. MetrumRG is now hosting all course materials from the Metrum Institute training series. c and d For round 3, the model selected from round 2 was brought forward. Metrum Research Group is proud to continue supporting training, education, and open courseware efforts in strategic modeling and simulation. b The model from round 1 was brought forward to round 2 the pharmacokinetic parameters which influenced the concentration–time profile of rolofylline were held fixed to those from round 1, and parameters which influenced the pharmacokinetics of M1-trans were optimized. a In round 1, only rolofylline data were considered. Compartments 1, 3, and 5 represent the first compartments for rolofylline, M1-trans, and M1-cis, respectively. The pharmacokinetic models considered during three rounds of exploratory pharmacokinetic modeling of rolofylline and metabolite data.
#Advan trans pk nonmem software
0 Global information - Software software : nonmem - Software version version : 7.3.0 - Run directory dir : data - Run file file : run001.lst - Run number run : run001 - Reference model ref : 000 - Run description descr : NONMEM PK example for xpose - Run start time timestart : Mon.
#Advan trans pk nonmem free
PREDPP - a powerful package of subroutines handling population PK data as well as general linear and nonlinear models, which can free the user from coding standard knetic type equations while simultaneously allowing complicated patient-type data to be easily analysed. Accordingly, the final model captured known aspects of rolofylline metabolism and was capable of simultaneously describing the PK of rolofylline and metabolites in healthy volunteers. summary (xpdb, problem 1) Summary for problem no. NONMEM ® itself, the basic and very general nonlinear regression programme. In addition, the final PK model contained provisions for both conversion of rolofylline to metabolites and stereochemical conversion of M1-trans to M1-cis. The simultaneous PK model comprised, in part, a two-compartment linear PK model for rolofylline, with estimates of clearance and volume of distribution at steady-state of 24.4 L/h and 239 L, respectively.
The rolofylline and metabolite data were analyzed simultaneously using NONMEM.
#Advan trans pk nonmem trial
Data included for this investigation came from a randomized, double-blind, dose-escalation trial in four groups of healthy volunteers (N=36) where single doses of rolofylline, spanning 1 to 60 mg ,were infused over 1-2 h. The aim of this investigation was to provide a pharmacokinetic (PK) model for rolofylline and metabolites following intravenous administration to healthy volunteers. Rolofylline is metabolized primarily to the pharmacologically active M1-trans and M1-cis metabolites (metabolites) by cytochrome P450 (CYP) 3A4. Rolofylline is a potent, selective adenosine A1 receptor antagonist that was under development for the treatment of patients with acute congestive heart failure and renal impairment.
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