Package ICSpkTS. R topics documented: September 4, Type Package

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1 Package ICSpkTS September 4, 2012 Type Package Title Simulation of pharmacokinetic trials after administration of inhaled corticosteroids. Version 1.0 Date Author Benjamin Weber Maintainer Benjamin Weber Description Simulation of pharmacokinetic (PK) trials after administration of inhaled corticosteroids (ICS). PK trials can be simulated in a parallel design after administration of two different hypothetical ICS, two different formulation of the same ICS, or the same formulation of an ICS in a different patient population. 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained. License GPL-3 R topics documented: ICSpkTS-package AUC.func BUD FLU FP ICS ICSPKmodel ICSPKmodel1Comp TA Index 19 1

2 2 AUC.func ICSpkTS-package Simulation of Pharmacokinetic Trials for Hypothetical Inhaled Corticosteroids Description Details Simulation of pharmacokinetic (PK) trials after administration of inhaled corticosteroids (ICS). PK trials can be simulated in a parallel design after administration of two different hypothetical ICS, two different formulation of the same ICS, or the same formulation of an ICS in a different patient population. 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained. Package: ICSpkTS Type: Package Version: 1.0 Date: License: GPL-3 Author(s) Benjamin Weber Maintainer: Benjamin Weber <benjaminweber@ufl.edu> See Also ICS, ICSPKmodel, ICSPKmodel1Comp, BUD, FLU, FP, TA AUC.func Function for Calculation of the Area under the Plasma Concentration Time Curve (AUC) Description Function for Calculation of the Area under the Plasma Concentration Time Curve (AUC) Usage AUC.func(x)

3 BUD 3 Arguments x List containing the observed plasma concentrations Author(s) Benjamin Weber Maintainer: Benjamin Weber <benjaminweber@ufl.edu> See Also ICSPKmodel Examples library(icspkts) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6) Conc = c(0.5,1.2,1.5,0.8,0.65,0.4,0.3,0.2,0.1) AUC.func(Conc) BUD Simulation of Pharmacokinetic (PK) Trials for Inhaled Budesonide Description This module enables the user to simulate PK trials for two (possibly) different formulations of inhaled budesonide. The (observed) plasma concentration time profiles of two hypothetical budesonide formulations can be compared (in a parallel study design) and 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained. Usage BUD(plots = FALSE, tables = FALSE) Arguments plots tables TRUE or FALSE (default), TRUE: plots will be created that display average and individual plasma concentration time profiles (PDF files). Plots will be saved in the current working directory. TRUE or FALSE (default), TRUE: tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) (CSV files). Tables will be saved in the current working directory.

4 4 BUD Note The number of subjects, the time points at which plasma samples are obtained, and all model parameters have to be specified before the function is run (see example). Drug specific model parameters (e.g., clearance and volume of distribution) are fixed to literature estimates and cannot be changed. All other model parameters are set to default values and can be altered by the user. Further information about the PK model, the model parameters, their interpretation, and their units is available (ICSPKmodel) Author(s) Benjamin Weber Maintainer: Benjamin Weber References Byron PR. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci. 1986;75: Krishnaswami S, Hochhaus G, Derendorf H. An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy. AAPS PharmSci. 2000;2: Ryrfeldt A, Andersson P, Edsbaecker S, Toennesson M, Davies D, Pauwels R. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl. 1982;122: Borgstrom L, Bondesson E, Moren F, Trofast E, Newman SP. Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects. Eur Respir J. 1994;7: Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J. 1994;7: Wildhaber JH, Devadason SG, Wilson JM, Roller C, Lagana T, Borgstrom L, et al. Lung deposition of budesonide from turbuhaler in asthmatic children. Eur J Pediatr. 1998;157: Kallen A, Thorsson L. Drug disposition analysis: a comparison between budesonide and fluticasone. J Pharmacokinet Pharmacodyn. 2003;30: Pitcairn G, Reader S, Pavia D, Newman S. Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler. J Aerosol Med. 2005;18: See Also Borgstrom L. Deposition patterns with Turbuhaler. J Aerosol Med. 1994;7:S ICSPKmodel, ICS, FLU, FP, TA Examples #Calling the ICSpkTS package library(icspkts) #Number of Subjects (n) per Group

5 BUD 5 n.subjects = 25 #Time points at which plasma samples are obtained (in h) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6,8,10,12,14,16,18,20,22,24) #Formulation A - Model Parameters - Typical Values (TV) and Dose.A = 500 TV.FLung.A = 0.3 TV.FC.A = 0.5 TV.kdiss.A = 17.8 TV.kmuc.A = TV.kpulC.A = 10 TV.kpulP.A = 20 BSV.FLung.A = 0.2 BSV.FC.A = 0.2 BSV.FBA.A = 0.2 BSV.kdiss.A = 0.2 BSV.kmuc.A = 0.2 BSV.kpulC.A = 0.2 BSV.kpulP.A = 0.2 BSV.ka.A = 0.2 BSV.CL.A = 0.2 BSV.VC.A = 0.2 BSV.k12.A = 0.2 BSV.k21.A = 0.2 #Formulation B - Model Parameters - Typical Values (TV) and Dose.B = 500 TV.FLung.B = 0.3 TV.FC.B = 0.5 TV.kdiss.B = 17.8 TV.kmuc.B = TV.kpulC.B = 10 TV.kpulP.B = 20 BSV.FLung.B = 0.2 BSV.FC.B = 0.2 BSV.FBA.B = 0.2 BSV.kdiss.B = 0.2 BSV.kmuc.B = 0.2 BSV.kpulC.B = 0.2 BSV.kpulP.B = 0.2

6 6 FLU BSV.ka.B = 0.2 BSV.CL.B = 0.2 BSV.VC.B = 0.2 BSV.k12.B = 0.2 BSV.k21.B = 0.2 #Within-Subject Variability (WSV) WSV = 0.3 #PK Trial Simulation BUD(plots=FALSE,tables=FALSE) FLU Simulation of Pharmacokinetic (PK) Trials for Inhaled Flunisolide Description Usage This module enables the user to simulate PK trials for two (possibly) different formulations of inhaled flunisolide. The (observed) plasma concentration time profiles of two hypothetical flunisolide formulations can be compared (in a parallel study design) and 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained. FLU(plots = FALSE, tables = FALSE) Arguments plots tables TRUE or FALSE (default), TRUE: plots will be created that display average and individual plasma concentration time profiles (PDF files). Plots will be saved in the current working directory. TRUE or FALSE (default), TRUE: tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) (CSV files). Tables will be saved in the current working directory. Note The number of subjects, the time points at which plasma samples are obtained, and all model parameters have to be specified before the function is run (see example). Drug specific model parameters (e.g., clearance and volume of distribution) are fixed to literature estimates and cannot

7 FLU 7 be changed. All other model parameters are set to default values and can be altered by the user. Further information about the PK model, the model parameters, their interpretation, and their units is available (ICSPKmodel) Author(s) Benjamin Weber Maintainer: Benjamin Weber <benjaminweber@ufl.edu> References Byron PR. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci. 1986;75: Krishnaswami S, Hochhaus G, Derendorf H. An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy. AAPS PharmSci. 2000;2: See Also ICSPKmodel, ICS, BUD, FP, TA Examples #Calling the ICSpkTS package library(icspkts) #Number of Subjects (n) per Group n.subjects = 25 #Time points at which plasma samples are obtained (in h) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6,8,10,12,14,16,18,20,22,24) #Formulation A - Model Parameters - Typical Values (TV) and Dose.A = 250 TV.FLung.A = 0.24 TV.FC.A = 0.5 TV.kdiss.A = 14 TV.kmuc.A = TV.kpulC.A = 10 TV.kpulP.A = 20 BSV.FLung.A = 0.2

8 8 FP BSV.FC.A = 0.2 BSV.FBA.A = 0.2 BSV.kdiss.A = 0.2 BSV.kmuc.A = 0.2 BSV.kpulC.A = 0.2 BSV.kpulP.A = 0.2 BSV.ka.A = 0.2 BSV.CL.A = 0.2 BSV.VC.A = 0.2 BSV.k12.A = 0.2 BSV.k21.A = 0.2 #Formulation B - Model Parameters - Typical Values (TV) and Dose.B = 250 TV.FLung.B = 0.24 TV.FC.B = 0.5 TV.kdiss.B = 14 TV.kmuc.B = TV.kpulC.B = 10 TV.kpulP.B = 20 BSV.FLung.B = 0.2 BSV.FC.B = 0.2 BSV.FBA.B = 0.2 BSV.kdiss.B = 0.2 BSV.kmuc.B = 0.2 BSV.kpulC.B = 0.2 BSV.kpulP.B = 0.2 BSV.ka.B = 0.2 BSV.CL.B = 0.2 BSV.VC.B = 0.2 BSV.k12.B = 0.2 BSV.k21.B = 0.2 #Within-Subject Variability (WSV) WSV = 0.3 #PK Trial Simulation FLU(plots=FALSE,tables=FALSE) FP Simulation of Pharmacokinetic (PK) Trials for Inhaled Fluticasone Propionate

9 FP 9 Description This module enables the user to simulate PK trials for two (possibly) different formulations of inhaled fluticasone propionate. The (observed) plasma concentration time profiles of two hypothetical fluticasone propionate formulations can be compared (in a parallel study design) and 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained. Usage FP(plots = FALSE, tables = FALSE) Arguments plots tables TRUE or FALSE (default), TRUE: plots will be created that display average and individual plasma concentration time profiles (PDF files). Plots will be saved in the current working directory. TRUE or FALSE (default), TRUE: tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) (CSV files). Tables will be saved in the current working directory. Note The number of subjects, the time points at which plasma samples are obtained, and all model parameters have to be specified before the function is run (see example). Drug specific model parameters (e.g., clearance and volume of distribution) are fixed to literature estimates and cannot be changed. All other model parameters are set to default values and can be altered by the user. Further information about the PK model, the model parameters, their interpretation, and their units is available (ICSPKmodel) Author(s) Benjamin Weber Maintainer: Benjamin Weber <benjaminweber@ufl.edu> References Byron PR. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci. 1986;75: Krishnaswami S, Hochhaus G, Derendorf H. An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy. AAPS PharmSci. 2000;2: Mollmann H, Wagner M, Krishnaswami S, Dimova H, Tang Y, Falcoz C, et al. Single-dose and steady-state pharmacokinetic and pharmacodynamic evaluation of therapeutically clinically equivalent doses of inhaled fluticasone propionate and budesonide, given as Diskus or Turbohaler drypowder inhalers to healthy subjects. J Clin Pharmacol. 2001;41:

10 10 FP Thorsson L, Edsbacker S, Kallen A, Lofdahl CG. Pharmacokinetics and systemic activity of fluticasone via Diskus and pmdi, and of budesonide via Turbuhaler. Br J Clin Pharmacol. 2001;52: Mackie AE, Ventresca GP, Fuller RW, Bye A. Pharmacokinetics of intravenous fluticasone propionate in healthy subjects. Br J Clin Pharmacol. 1996;41: Krishnaswami S, Hochhaus G, Mollmann H, Barth J, Derendorf H. Interpretation of absorption rate data for inhaled fluticasone propionate obtained in compartmental pharmacokinetic modeling. Int J Clin Pharmacol Ther. 2005;43: See Also ICSPKmodel, ICS, BUD, FLU, TA Examples #Calling the ICSpkTS package library(icspkts) #Number of Subjects (n) per Group n.subjects = 25 #Time points at which plasma samples are obtained (in h) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6,8,10,12,14,16,18,20,22,24) #Formulation A - Model Parameters - Typical Values (TV) and Dose.A = 500 TV.FLung.A = 0.16 TV.FC.A = 0.5 TV.kdiss.A = TV.kmuc.A = TV.kpulC.A = 10 TV.kpulP.A = 20 BSV.FLung.A = 0.2 BSV.FC.A = 0.2 BSV.kdiss.A = 0.2 BSV.kmuc.A = 0.2 BSV.kpulC.A = 0.2 BSV.kpulP.A = 0.2 BSV.CL.A = 0.2 BSV.VC.A = 0.2 BSV.k12.A = 0.2

11 ICS 11 BSV.k21.A = 0.2 #Formulation B - Model Parameters - Typical Values (TV) and Dose.B = 500 TV.FLung.B = 0.16 TV.FC.B = 0.5 TV.kdiss.B = TV.kmuc.B = TV.kpulC.B = 10 TV.kpulP.B = 20 BSV.FLung.B = 0.2 BSV.FC.B = 0.2 BSV.kdiss.B = 0.2 BSV.kmuc.B = 0.2 BSV.kpulC.B = 0.2 BSV.kpulP.B = 0.2 BSV.CL.B = 0.2 BSV.VC.B = 0.2 BSV.k12.B = 0.2 BSV.k21.B = 0.2 #Within-Subject Variability (WSV) WSV = 0.3 #PK Trial Simulation FP(plots=FALSE,tables=FALSE) ICS Simulation of Pharmacokinetic (PK) Trials for Hypothetical Inhaled Corticosteroids (ICS) Description This module enables the user to simulate PK trials for hypothetical ICS. The (observed) plasma concentration time profiles of two hypothetical ICS can be compared (in a parallel study design) and 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained.

12 12 ICS Usage ICS(plots = FALSE, tables = FALSE) Arguments plots tables TRUE or FALSE (default), TRUE: plots will be created that display average and individual plasma concentration time profiles (PDF files). Plots will be saved in the current working directory. TRUE or FALSE (default), TRUE: tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) (CSV files). Tables will be saved in the current working directory. Note The number of subjects, the time points at which plasma samples are obtained, and all model parameters have to be specified before the function is run (see example). Further information about the PK model, the model parameters, their interpretation, and their units is available (ICSPKmodel) Author(s) Benjamin Weber Maintainer: Benjamin Weber <benjaminweber@ufl.edu> See Also ICSPKmodel, BUD, FLU, FP, TA Examples #Calling the ICSpkTS package library(icspkts) #Number of Subjects (n) per Group n.subjects = 25 #Time points at which plasma samples are obtained (in h) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6,8,10,12,14,16,18,20,22,24) #Situation A - Model Parameters - Typical Values (TV) and

13 ICS 13 Dose.A = 500 TV.FLung.A = 0.2 TV.FC.A = 0.5 TV.FBA.A = 0.1 TV.kdiss.A = 0.3 TV.kmuc.A = 0.5 TV.kpulC.A = 0.4 TV.kpulP.A = 0.4 TV.ka.A = 0.65 TV.CL.A = 49 TV.VC.A = 87 TV.k12.A = 0.1 TV.k21.A = 0.05 BSV.FLung.A = 0.2 BSV.FC.A = 0.2 BSV.FBA.A = 0.2 BSV.kdiss.A = 0.2 BSV.kmuc.A = 0.2 BSV.kpulC.A = 0.2 BSV.kpulP.A = 0.2 BSV.ka.A = 0.2 BSV.CL.A = 0.2 BSV.VC.A = 0.2 BSV.k12.A = 0.2 BSV.k21.A = 0.2 #Situation B - Model Parameters - Typical Values (TV) and Dose.B = 500 TV.FLung.B = 0.2 TV.FC.B = 0.5 TV.FBA.B = 0.1 TV.kdiss.B = 0.3 TV.kmuc.B = 0.5 TV.kpulC.B = 0.4 TV.kpulP.B = 0.4 TV.ka.B = 0.65 TV.CL.B = 49 TV.VC.B = 87 TV.k12.B = 0.1 TV.k21.B = 0.05 BSV.FLung.B = 0.2 BSV.FC.B = 0.2 BSV.FBA.B = 0.2 BSV.kdiss.B = 0.2 BSV.kmuc.B = 0.2 BSV.kpulC.B = 0.2 BSV.kpulP.B = 0.2 BSV.ka.B = 0.2 BSV.CL.B = 0.2

14 14 ICSPKmodel BSV.VC.B = 0.2 BSV.k12.B = 0.2 BSV.k21.B = 0.2 #Within-Subject Variability (WSV) WSV = 0.3 #PK Trial Simulation ICS(plots=FALSE,tables=FALSE) ICSPKmodel Deterministic Pharmacokinetic (PK) Model that Describes the Plasma Concentration Time Profile of Inhaled Corticosteroids (ICS) Description Deterministic PK model that describes the plasma concentration time profile of inhaled corticosteroids Usage ICSPKmodel(PKparms=list(Dose,FLung,FC,FBA,kdiss,kmuc,kpulC,kpulP,ka,CL,VC,k12,k21)) Arguments PKparms Dose FLung FC FBA kdiss kpulc kpulp ka CL VC k12 k21 List containing the parameter values for the deterministic PK model By inhaler emitted dose (mcg) Fraction of the emitted dose that is deposited in the lung Fraction of the lung dose that is deposited in central lung regions Oral bioavailability of the ICS Dissolution rate constant of the ICS (1/h) Absorption rate constant from central lung regions into the systemic circulation (1/h) Absorption rate constant from peripheral lung regions into the systemic circulation (1/h) Absorption rate constant from the gastrointestinal tract into the systemic circulation (1/h) Systemic clearance of the ICS (L/h) Volume of distribution of the central body compartment of the ICS (L) Distribution rate constant (1/h) Distribution rate constant (1/h)

15 ICSPKmodel1Comp 15 Author(s) Benjamin Weber Maintainer: Benjamin Weber See Also ICS Examples library(icspkts) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6) PKparms = c(500,0.2,0.5,0.1,0.3,0.5,0.4,0.4,0.65,49,87,0.1,0.05) ICSPKmodel(PKparms) ICSPKmodel1Comp Deterministic Pharmacokinetic (PK) Model that Describes the Plasma Concentration Time Profile of Inhaled Corticosteroids (ICS) for a One-Compartment Body Model Description Deterministic PK Model that describes the plasma concentration time profile of inhaled corticosteroids for a one-compartment body model Usage ICSPKmodel1Comp(PKparms=list(Dose,FLung,FC,FBA,kdiss,kmuc,kpulC,kpulP,ka,CL,VC)) Arguments PKparms Dose FLung FC FBA kdiss kpulc kpulp ka CL VC List containing the parameter values for the deterministic PK model By inhaler emitted dose (mcg) Fraction of the emitted dose that is deposited in the lung Fraction of the lung dose that is deposited in central lung regions Oral bioavailability of the ICS Dissolution rate constant of the ICS (1/h) Absorption rate constant from central lung regions into the systemic circulation (1/h) Absorption rate constant from peripheral lung regions into the systemic circulation (1/h) Absorption rate constant from the gastrointestinal tract into the systemic circulation (1/h) Systemic clearance of the ICS (L/h) Volume of distribution of the central body compartment of the ICS (L)

16 16 TA Author(s) Benjamin Weber Maintainer: Benjamin Weber See Also ICS Examples library(icspkts) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6) PKparms = c(500,0.2,0.5,0.1,0.3,0.5,0.4,0.4,0.65,49,87) ICSPKmodel1Comp(PKparms) TA Simulation of Pharmacokinetic (PK) Trials for Inhaled Triamcinolone Acetonide Description This module enables the user to simulate PK trials for two (possibly) different formulations of inhaled triamcinolone acetonide. The (observed) plasma concentration time profiles of two hypothetical triamcinolone acetonide formulations can be compared (in a parallel study design) and 90 % confidence intervals of the geometric means ratios for the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax) will be calculated. Individual and average plasma concentration time profile plots as well as tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) can be optionally obtained. Usage TA(plots = FALSE, tables = FALSE) Arguments plots tables TRUE or FALSE (default), TRUE: plots will be created that display average and individual plasma concentration time profiles (PDF files). Plots will be saved in the current working directory. TRUE or FALSE (default), TRUE: tables containing the individual and average plasma concentration time data and the individual PK parameters (e.g., clearance, volume of distribution, absorption rate constant, lung deposition) and PK metrics (AUC, Cmax) (CSV files). Tables will be saved in the current working directory.

17 TA 17 Note The number of subjects, the time points at which plasma samples are obtained, and all model parameters have to be specified before the function is run (see example). Drug specific model parameters (e.g., clearance and volume of distribution) are fixed to literature estimates and cannot be changed. All other model parameters are set to default values and can be altered by the user. Further information about the PK model, the model parameters, their interpretation, and their units is available (ICSPKmodel1Comp) Author(s) Benjamin Weber Maintainer: Benjamin Weber See Also ICSPKmodel1Comp, ICS, BUD, FLU, FP Examples #Calling the ICSpkTS package library(icspkts) #Number of Subjects (n) per Group n.subjects = 25 #Time points at which plasma samples are obtained (in h) Time = c(0.17,0.33,0.5,1,1.5,2,3,4,6,8,10,12,14,16,18,20,22,24) #Formulation A - Model Parameters - Typical Values (TV) and Dose.A = 100 TV.FLung.A = 0.15 TV.FC.A = 0.5 TV.kdiss.A = 1.2 TV.kmuc.A = TV.kpulC.A = 10 TV.kpulP.A = 20 BSV.FLung.A = 0.2 BSV.FC.A = 0.2 BSV.FBA.A = 0.2 BSV.kdiss.A = 0.2

18 18 TA BSV.kmuc.A = 0.2 BSV.kpulC.A = 0.2 BSV.kpulP.A = 0.2 BSV.ka.A = 0.2 BSV.CL.A = 0.2 BSV.VC.A = 0.2 #Formulation B - Model Parameters - Typical Values (TV) and Dose.B = 100 TV.FLung.B = 0.15 TV.FC.B = 0.5 TV.kdiss.B = 1.2 TV.kmuc.B = TV.kpulC.B = 10 TV.kpulP.B = 20 BSV.FLung.B = 0.2 BSV.FC.B = 0.2 BSV.FBA.B = 0.2 BSV.kdiss.B = 0.2 BSV.kmuc.B = 0.2 BSV.kpulC.B = 0.2 BSV.kpulP.B = 0.2 BSV.ka.B = 0.2 BSV.CL.B = 0.2 BSV.VC.B = 0.2 #Within-Subject Variability (WSV) WSV = 0.3 #PK Trial Simulation TA(plots=FALSE,tables=FALSE)

19 Index Topic Budesonide BUD, 3 Topic Compartment Model AUC.func, 2 BUD, 3 FLU, 6 FP, 8 ICS, 11 ICSPKmodel, 14 ICSPKmodel1Comp, 15 ICSpkTS-package, 2 TA, 16 Topic Flunisolide FLU, 6 Topic Fluticasone Propionate FP, 8 Topic Inhaled Corticosteroids AUC.func, 2 BUD, 3 FLU, 6 FP, 8 ICS, 11 ICSPKmodel, 14 ICSPKmodel1Comp, 15 ICSpkTS-package, 2 TA, 16 Topic PK Trial Simulations AUC.func, 2 BUD, 3 FLU, 6 FP, 8 ICS, 11 ICSPKmodel, 14 ICSPKmodel1Comp, 15 ICSpkTS-package, 2 TA, 16 Topic Triamcinolone Acetonide TA, 16 FP, 2, 4, 7, 8, 12, 17 ICS, 2, 4, 7, 10, 11, ICSPKmodel, 2 4, 7, 9, 10, 12, 14 ICSPKmodel1Comp, 2, 15, 17 ICSpkTS (ICSpkTS-package), 2 ICSpkTS-package, 2 TA, 2, 4, 7, 10, 12, 16 AUC.func, 2 BUD, 2, 3, 7, 10, 12, 17 FLU, 2, 4, 6, 10, 12, 17 19