Package {pkr}

Pharmacokinetics in R

Description

It conducts a noncompartmental analysis(NCA) as closely as possible to the most widely used commercial pharmacokinetic analysis software.

Details

The main functions are

NCA	     to perform NCA for many subjects.

IndiNCA  to perform NCA for one subject.

Author(s)

Kyun-Seop Bae <k@acr.kr>, Jee Eun Lee <JeeEun.Lee@fda.hhs.gov>

References

1. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

2. Shargel L, Yu A. Applied Biopharmaceutics and Pharmacokinetics. 7th ed. 2015.

3. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. 2011.

4. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. revised and expanded. 1982.

Examples

# Theoph and Indometh data: dose in mg, conc in mg/L, time in h
NCA(Theoph, "Subject", "Time", "conc", dose=320, uConc="mg/L")
NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", uConc="mg/L")

iAUC = data.frame(Name=c("AUC[0-12h]","AUC[0-24h]"), Start=c(0,0), End=c(12,24)) ; iAUC
NCA(Theoph, "Subject", "Time", "conc", dose=320, iAUC=iAUC, uConc="mg/L")
NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", iAUC=iAUC, uConc="mg/L")

# writeLines(NCA(Theoph, "Subject", "Time", "conc", dose=320, report="Text", uConc="mg/L"),
#            "Theoph_Linear_CoreOutput.txt")
# writeLines(NCA(Theoph, "Subject", "Time", "conc", dose=320, fit="Log", report="Text",
#            uConc="mg/L"), "Theoph_Log_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", report="Text",
#            uConc="mg/L"), "Indometh_Bolus_Linear_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", fit="Log",
#            report="Text", uConc="mg/L"), "Indometh_Bolus_Log_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Infusion", dur=0.25,
#            report="Text", uConc="mg/L"), "Indometh_Infusion_Linear_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Infusion", dur=0.25,
#            fit="Log", report="Text", uConc="mg/L"), "Indometh_Infusion_Log_CoreOutput.txt")

sNCA(Theoph[Theoph$Subject==1,"Time"], Theoph[Theoph$Subject==1, "conc"], dose=320, concUnit="mg/L")
sNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Bolus", concUnit="mg/L")
sNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Infusion", dur=0.25, concUnit="mg/L")

iAUC = data.frame(Name=c("AUC[0-12h]","AUC[0-24h]"), Start=c(0,0), End=c(12,24)) ; iAUC
sNCA(Theoph[Theoph$Subject==1,"Time"], Theoph[Theoph$Subject==1, "conc"], dose=320,
        iAUC=iAUC, concUnit="mg/L")
sNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Bolus", iAUC=iAUC, concUnit="mg/L")
sNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Infusion", dur=0.25, iAUC=iAUC, concUnit="mg/L")

Calculate Area Under the Curve (AUC) and Area Under the first Moment Curve (AUMC) in a table format

Description

Calculate Area Under the Curve(AUC) and the first Moment Curve(AUMC) in two ways; 'linear trapezoidal method' or 'linear-up and log-down' method. Return a table of cumulative values.

Usage

AUC(x, y, down = "Linear")

Arguments

Details

down="Linear" means linear trapezoidal rule with linear interpolation. down="Log" means linear-up and log-down method.

Value

Table with two columns, AUC and AUMC; the first column values are cumulative AUCs and the second column values cumulative AUMCs.

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. pp687-689. 2011.

See Also

LinAUC, LogAUC

Examples

AUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"])
AUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"], down="Log")

Internal Functions

Description

Internal functions

Details

These are not to be called by the user.

Choose best fit slope for the log(y) and x regression by the criteria of adjusted R-square

Description

It sequentially fits (log(y) ~ x) from the last point of x to the previous points with at least 3 points. It chooses a slope the highest adjusted R-square. If the difference is less then 1e-4, it chooses longer slope.

Usage

BestSlope(x, y, adm = "Extravascular", TOL=1e-4)

Arguments

Details

Choosing the best terminal slope (y in log scale) in pharmacokinetic analysis is somewhat challenging, and it could vary by analysis performer. Pheonix WinNonlin chooses a slope with highest adjusted R-squared and the longest one. Difference of adjusted R-Squared less than TOL considered to be 0. This function uses ordinary least square method (OLS).

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

Slope

Examples

BestSlope(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"])
BestSlope(Indometh[Indometh$Subject==1, "time"], Indometh[Indometh$Subject==1, "conc"],
          adm="Bolus")

Noncompartmental Analysis for an Individual

Description

It performs a noncompartmental analysis with one subject data. This will be deprecated. Use sNCA() instead.

Usage

IndiNCA(x, y, dose = 0, fit = "Linear", adm = "Extravascular", dur = 0,
               report = "Table", iAUC = "", uTime = "h", uConc = "ug/L", uDose = "mg")

Arguments

Details

This performs a noncompartmental analysis for a subject. It returns practically the same result with the most popular commercial software.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

1. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

2. Shargel L, Yu A. Applied Biopharmaceutics and Pharmacokinetics. 7th ed. 2015.

3. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. 2011.

4. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. revised and expanded. 1982.

See Also

AUC, BestSlope

Examples

IndiNCA(Theoph[Theoph$Subject==1,"Time"], Theoph[Theoph$Subject==1, "conc"], dose=320, uConc="mg/L")
IndiNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Bolus", uConc="mg/L")
IndiNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Infusion", dur=0.25, uConc="mg/L")

IndiNCA(Theoph[Theoph$Subject==1,"Time"], Theoph[Theoph$Subject==1, "conc"], dose=320,
        report="Text", uConc="mg/L")
IndiNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Bolus", report="Text", uConc="mg/L")
IndiNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Infusion", dur=0.25, report="Text", uConc="mg/L")

iAUC = data.frame(Name=c("AUC[0-12h]","AUC[0-24h]"), Start=c(0,0), End=c(12,24)) ; iAUC
IndiNCA(Theoph[Theoph$Subject==1,"Time"], Theoph[Theoph$Subject==1, "conc"], dose=320,
        iAUC=iAUC, uConc="mg/L")
IndiNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Bolus", iAUC=iAUC, uConc="mg/L")
IndiNCA(Indometh[Indometh$Subject==1,"time"], Indometh[Indometh$Subject==1, "conc"], dose=25,
        adm="Infusion", dur=0.25, iAUC=iAUC, uConc="mg/L")

Calculate interval AUC

Description

It calculates interval AUC

Usage

IntAUC(x, y, t1, t2, Res, down = "Linear")

Arguments

Details

This calculates an interval (partial) AUC (from t1 to t2) with the given series of x and y. If t1 and/or t2 cannot be found within x vector, it interpolates according to the down option.

Value

return interval AUC value (scalar)

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

1. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

2. Shargel L, Yu A. Applied Biopharmaceutics and Pharmacokinetics. 7th ed. 2015.

3. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. 2011.

4. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. revised and expanded. 1982.

See Also

AUC, Interpol

Examples

Res = sNCA(Theoph[Theoph$Subject==1,"Time"], Theoph[Theoph$Subject==1, "conc"], 
           dose=320, concUnit="mg/L")
IntAUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"], t1=0.5, t2=11, Res)

Interpolate y value

Description

It interpolates y value when a corresponding x value (xnew) does not exist within x vector

Usage

Interpol(x, y, xnew, Slope, b0, down = "Linear")

Arguments

Details

This function interpolate y value, if xnew is not in x vector. If xnew is in x vector, it just returns the given x and y vector. This function usually is called by IntAUC function Returned vector is sorted in the order of increasing x values.

Value

new x and y vector containing xnew and ynew point

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

IntAUC

Examples

x = 10:1 + 0.1
y = -2*x + 40.2
Interpol(x, y, 1.5)
Interpol(x, y, 1.5, down="Log")

Area Under the Curve(AUC) and Area Under the first Moment Curve(AUMC) by linear trapezoidal method

Description

It calculates AUC and AUMC using linear trapezoidal method

Usage

LinAUC(x, y)

Arguments

Details

This function returns AUC and AUMC by linear trapezoidal method.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

1. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

2. Shargel L, Yu A. Applied Biopharmaceutics and Pharmacokinetics. 7th ed. 2015.

3. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. 2011.

4. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. revised and expanded. 1982.

See Also

LogAUC, AUC

Examples

LinAUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"])
AUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"]) # compare the last line

Area Under the Curve(AUC) and Area Under the first Moment Curve(AUMC) by linear-up log-down method

Description

It calculates AUC and AUMC using linear-up log-down method

Usage

LogAUC(x, y)

Arguments

Details

This function returns AUC and AUMC by linear-up log-down method.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

1. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

2. Shargel L, Yu A. Applied Biopharmaceutics and Pharmacokinetics. 7th ed. 2015.

3. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. 2011.

4. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. revised and expanded. 1982.

See Also

LinAUC,AUC

Examples

LogAUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"])
# Compare the last line with the above
AUC(Theoph[Theoph$Subject==1, "Time"], Theoph[Theoph$Subject==1, "conc"], down="Log") 

Noncompartmental analysis for a dataset with multiple subjects

Description

conduct noncompartmental analysis for many subjects in a data table

Usage

NCA(concData, id, Time, conc, trt="", fit = "Linear", dose = 0, 
           adm = "Extravascular", dur = 0, report = "Table", iAUC = "", 
           uTime = "h", uConc = "ug/L", uDose = "mg")

Arguments

Details

This function calls sNCA repeatedly to do NCA for each subject. If you specify report="Text", this function returns in free text format to be used in a report file.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

1. Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

2. Shargel L, Yu A. Applied Biopharmaceutics and Pharmacokinetics. 7th ed. 2015.

3. Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. 4th ed. 2011.

4. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. revised and expanded. 1982.

See Also

sNCA

Examples

# Theoph and Indometh data: dose in mg, conc in mg/L, time in h
NCA(Theoph, "Subject", "Time", "conc", dose=320, uConc="mg/L")
NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", uConc="mg/L")

iAUC = data.frame(Name=c("AUC[0-12h]","AUC[0-24h]"), Start=c(0,0), End=c(12,24)) ; iAUC
NCA(Theoph, "Subject", "Time", "conc", dose=320, iAUC=iAUC, uConc="mg/L")
NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", iAUC=iAUC, uConc="mg/L")

# writeLines(NCA(Theoph, "Subject", "Time", "conc", dose=320, report="Text", uConc="mg/L"),
#            "Theoph_Linear_CoreOutput.txt")
# writeLines(NCA(Theoph, "Subject", "Time", "conc", dose=320, fit="Log", report="Text", 
#            uConc="mg/L"), "Theoph_Log_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", report="Text", 
#            uConc="mg/L"), "Indometh_Bolus_Linear_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Bolus", fit="Log",
#            report="Text", uConc="mg/L"), "Indometh_Bolus_Log_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Infusion", dur=0.25,
#            report="Text", uConc="mg/L"), "Indometh_Infusion_Linear_CoreOutput.txt")
# writeLines(NCA(Indometh, "Subject", "time", "conc", dose=25, adm="Infusion", dur=0.25,
#            fit="Log", report="Text", uConc="mg/L"), "Indometh_Infusion_Log_CoreOutput.txt")

NCA of SDTM data for single subject

Description

This performs Noncompartmental Analysis(NCA) for one dosing record from the CDISC EX and PC domain.

Usage

NCA0(EX0, PC0, fit="Linear", excludeInfusion=TRUE, label="")

Arguments

Details

The administration method is taken from EXROUTE first: an EXROUTE of "INTRAVENOUS" gives "Infusion" when EXENDTC is later than EXSTDTC and "Bolus" otherwise, and any other route gives "Extravascular". Time after dose is computed from EXSTDTC and negative values are set to zero, so a pre-dose sample is placed at time zero.

This calls sNCA. This is called by rNCA function.

Value

This returns a named character vector: AdmMethod, Dose, UnitDose, Dur, UnitTime, UnitConc, followed by the NCA parameters. Which parameters are present depends on the administration method.

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, rNCA, sNCA

Round Half Away from Zero

Description

This is an ordinary rounding function, so called round half away from zero

Usage

Round(x, n = 0)

Arguments

Details

The function round in R base rounds to the even number, i.e. round(0.5) is 0 not 1. If you want rounding 0.5 be 1, you can use this Round function. This function is for the consistency with other software like MS-Excel, SAS.

Value

ordinarily rounded value

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

See wikipedia subject "Rounding"

Examples

(x = 1:10 - 0.5)
Round(x)
round(x) # compare with the above

NCA Report Configuation Table

Description

Contains the names and order of colum of return table/text by IndiNCA and NCA functions

Usage

RptCfg

Format

A data frame with 48 observations on the following 10 variables.

PPTESTCD

a character vector of CDISC SDTM PPTESTCD

SYNONYM

a character vector of CDISC SDTM PPTESTCD Synonym

NCI

a character vector of NCI peferred terms

WNL

a character vector of WinNonlin(R) software variables

ExtravascularDefault

a numeric vector of ordering in report for extravascular administration, Zero means exclusion in the report.

ExtravascularWNL

a numeric vector of WinNonlin(R) style ordering in report for extravascular administration, Zero means exclusion in the report.

BolusDefault

a numeric vector of ordering in report for extravascular administration, Zero means exclusion in the report.

BolusWNL

a numeric vector of WinNonlin(R) style ordering in report for extravascular administration, Zero means exclusion in the report.

InfusionDefault

a numeric vector of ordering in report for extravascular administration, Zero means exclusion in the report.

InfusionWNL

a numeric vector of WinNonlin(R) style ordering in report for extravascular administration, Zero means exclusion in the report.

Details

This table should exist in pkr package. User can edit this table for shaping the report in one's own style.

Get the Slope of regression log(y) ~ x

Description

It calculates the slope with linear regression of log(y) ~ x

Usage

Slope(x, y)

Arguments

Details

With time-concentration curve, you frequently need to estimate slope in log(concentration) ~ time. This function is usually called by BestSlope function and you seldom need to call this function directly.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

BestSlope

Examples

Slope(Indometh[Indometh$Subject==1, "time"], Indometh[Indometh$Subject==1, "conc"])

Internal Functions

Description

Internal functions

Details

These are not to be called by the user.

Internal Functions

Description

Internal functions

Details

These are not to be called by the user.

Disply CDISC standard units and multiplied factor of NCA results

Description

It displays CDISC PP output units and multiplication factor for them.

Usage

Unit(code = "", timeUnit = "h", concUnit = "ng/mL", doseUnit = "mg", MW = 0)

Arguments

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

Examples

Unit(concUnit="ug/L", doseUnit="mg")
Unit(concUnit="ng/L", doseUnit="mg")

Unit(concUnit="umol/L", doseUnit="mmol")
Unit(concUnit="nmol/L", doseUnit="mmol")

Unit(concUnit="mmol/L", doseUnit="mg", MW=500)
Unit(concUnit="umol/L", doseUnit="mg", MW=500)
Unit(concUnit="nmol/L", doseUnit="mg", MW=500)
Unit(concUnit="nmol/mL", doseUnit="mg", MW=500)

Unit(concUnit="ug/L", doseUnit="mmol", MW=500)
Unit(concUnit="ug/L", doseUnit="mol", MW=500)
Unit(concUnit="ng/L", doseUnit="mmol", MW=500)
Unit(concUnit="ng/mL", doseUnit="mmol", MW=500)

Unit(concUnit="nmol/L", doseUnit="mg")
Unit(concUnit="ug/L", doseUnit="mmol")

Combine XPT files

Description

This function combines specified CDISC domain XPT files across the folders.

Usage

combXPT(folders, domain)

Arguments

Details

You need to designate only one CDISC domain name. You may specify one or more folders to find the domain XPT files.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, readEX, readPC

Convert intermeidate NCA result to adequate unit.

Description

This is an internal function

Author(s)

Kyun-Seop Bae <k@acr.kr>

Forest plot to compare NCA results

Description

This function compares NCA results usually from rNCA function

Usage

foreNCA(NCAres = "", PPTESTCD = "", PCTESTCD = "", title = "", ...)

Arguments

Details

This functio calls forestplot in forest package.

Value

Currently, this just plots.

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, rNCA

Load EX and PC domain files in folders

Description

This loads and returns EX and PC domain files in the specified folders

Usage

loadEXPC(folders)

Arguments

Details

This reads EX and PC domain files in the specified folder. This calls readEX and readPC functions.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, readEX, readPC

NCA output to pdf file

Description

This output NCA result in a pdf file.

Usage

pdfNCA(fileName = "Temp-NCA.pdf", concData, colSubj = "Subject", colTime = "Time", 
       colConc = "conc", dose = 0, adm = "Extravascular", dur = 0, doseUnit = "mg", 
       timeUnit = "h", concUnit = "ug/L", down="Linear", MW = 0)

Arguments

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, txtNCA, rtfNCA

Examples

#pdfNCA(fileName="NCA-Theoph.pdf", Theoph, colSubj="Subject", colTime="Time", 
#       colConc="conc", dose=320, doseUnit="mg", timeUnit="h", concUnit="mg/L")
#pdfNCA(fileName="NCA-Indometh.pdf", Indometh, colSubj="Subject", colTime="time", 
#       colConc="conc", adm="Infusion", dur=0.5, dose=25, doseUnit="mg", 
#       timeUnit="h", concUnit="mg/L")

Plot best fit slope

Description

Automatically select best fit slope for the given x(usually time) and log(y)(usually concentration) values.

Usage

plotFit(concData, id, Time, conc, mol = "", adm = "Extravascular", ID = "", Mol = "")

Arguments

Details

Find the best fit slope then plot it. Currently this function uses ordinary least square method(OLS) only. This function calles BestSlope function.

Value

Author(s)

Jee Eun Lee <JeeEun.Lee@fda.hhs.gov>

See Also

BestSlope

Examples

plotFit(Theoph, "Subject", "Time", "conc", ID="1")
plotFit(Indometh, "Subject", "time", "conc", adm="Bolus", ID="1")

Plot concentration vs. time curve for individuals and collectively.

Description

Generates individual and superposed concentration vs. time curves and saves them in pdf and tiff files.

Usage

plotPK(concData, id, Time, conc, unitTime = "hr", unitConc = "ng/mL", trt = "",
       fit = "Linear", dose = 0, adm = "Extravascular", dur = 0, outdir = "Output",
       name = "")

Arguments

Details

This function generates five figures: individual linear and semi-logarithmic profiles (one pdf each, several panels per page) and pooled linear, semi-logarithmic and mean with 95% confidence interval profiles (one tiff each, or png where the R build has no tiff device).

Each subject gets its own colour and plotting symbol whatever the number of subjects, and the subject legend is drawn in a panel of its own so that it cannot overlap the curves. When there are more subjects than can be labelled legibly, the count is shown instead of an unreadable legend. Treatment panels are laid out in a grid of at most four columns, so a study with many treatments neither exhausts the figure margins nor produces an enormous raster.

Non-finite times and concentrations are dropped from the axis ranges, and the semi-logarithmic figures use only positive concentrations. The semi-logarithmic axis is aligned to whole decades enclosing the data, so a labelled tick is always visible.

This function calls NCA().

Value

Invisibly, a character vector of the paths written. The files are saved in the outdir folder.

Author(s)

Jee Eun Lee <JeeEun.Lee@fda.hhs.gov>, Kyun-Seop Bae <k@acr.kr>

See Also

NCA

Examples

# plotPK(Theoph, "Subject", "Time", "conc", unitTime="hr", unitConc="mg/L", dose=320)
# plotPK(Indometh, "Subject", "time", "conc", unitTime="hr", unitConc="mg/L", adm="Bolus", dose=25)

Do NCA for review

Description

This performs NCA from the CDISC EX and PC datasets.

Usage

rNCA(ex, pc, study = "", trt = "", id = "", analyte = "",
     codeBQL = c("< 0", "<0", "NQ", "BLQ", "BQL", "BQoL", "<LOQ"),
     fit="Linear", MinPoints = 5, excludeInfusion = TRUE)

Arguments

Details

One row of result is produced for each subject, dosing interval and analyte. A dosing interval starts at its own EXSTDTC and ends at the subject's next real dose of any treatment in the same study, so that in a crossover trial the first period is not extended into the second; a placebo or zero dose delivers no drug and does not end an interval. The final interval is open-ended, so terminal and follow-up samples still contribute to the elimination phase.

The last concentration in the 24 hours before the dose is carried into the interval as the pre-dose sample, and placed at time zero. The lookback is bounded because an unbounded one would report a sample from an earlier period as this dose's initial concentration. In an interval that is followed by another dose the trailing trough is dropped when its nominal time (PCTPTNUM) equals the pre-dose one, so that it is not counted twice.

EX and PC records are sorted by date and time before use, so the result does not depend on the row order of the input. Records whose date and time cannot be read as a full YYYY-MM-DDTHH:MM:SS value are dropped with a warning naming the subjects affected.

The automatic terminal-slope search restricts itself to samples after the maximum concentration. That is the right rule for an extravascular dose but says nothing about an infusion, so a sample drawn while drug is still being infused can win on adjusted R-squared and be reported as terminal elimination. Because a terminal phase does not exist while drug is still going in, excludeInfusion defaults to TRUE: the search is given only the samples after the end of infusion, and the same maximum-adjusted-R-squared criterion then selects the window among them; within that window it still starts after the largest of those samples. Set excludeInfusion=FALSE for the unrestricted search over all samples.

Only lambda z and the parameters derived from it (half-life, AUCIFO, AUCPEO, Vz) are affected - Cmax, AUClast and the other observed parameters cannot change. When there are too few post-infusion samples to fit a slope, a warning names the profile and the unrestricted selection is used, so no profile is lost silently.

The restriction applies to this function and to NCA0, which know the dosing record and so the end of infusion. sNCA and tblNCA take times and concentrations without a dosing record and remain faithful wrappers around NonCompart; give sNCA an explicit UsePoints to fix the window there.

This calls NCA0. Results of this can be further processed by foreNCA to plot and compare between studies and dose groups.

Value

This returns a table of NCA results, or invisibly NULL with a warning when no subject meets the MinPoints criterion.

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, NCA0, loadEXPC, foreNCA

Read EX domain files

Description

This reads EX domain files from the specified folders.

Usage

readEX(folders)

Arguments

Details

This calls combXPT function. This is called by loadEXPC function.

Value

This returns combined table of EX doamin.

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, combXPT, loadEXPC

Read PC domain files

Description

This reads PC domain files from the specified folders.

Usage

readPC(folders)

Arguments

Details

This calls combXPT function. This is called by loadEXPC function.

Value

This returns combined table of PC doamin.

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, combXPT, loadEXPC

NCA output to rtf file

Description

This output NCA result in a rtf file.

Usage

rtfNCA(fileName = "Temp-NCA.rtf", concData, colSubj = "Subject", colTime = "Time", 
       colConc = "conc", dose = 0, adm = "Extravascular", dur = 0, doseUnit = "mg", 
       timeUnit = "h", concUnit = "ug/L", down="Linear", MW = 0)

Arguments

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, txtNCA, pdfNCA

Examples

#rtfNCA(fileName="NCA-Theoph.rtf", Theoph, colSubj="Subject", colTime="Time", 
#       colConc="conc", dose=320, doseUnit="mg", timeUnit="h", concUnit="mg/L")
#rtfNCA(fileName="NCA-Indometh.rtf", Indometh, colSubj="Subject", colTime="time", 
#       colConc="conc", adm="Infusion", dur=0.5, dose=25, doseUnit="mg", 
#       timeUnit="h", concUnit="mg/L")

Simplest NCA

Description

This is the work-horse function for NCA.

Usage

sNCA(x, y, dose = 0, adm = "Extravascular", dur = 0, doseUnit = "mg", timeUnit = "h",
     concUnit = "ug/L", iAUC = "", down = "Linear", MW = 0, returnNA = TRUE,
     UsePoints = NULL)

Arguments

Details

This will replace IndiNCA.

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

References

Gabrielsson J, Weiner D. Pharmacokinetic and Pharmacodynamic Data Analysis - Concepts and Applications. 5th ed. 2016.

See Also

help, tblNCA

Examples

# For one subject
x = Theoph[Theoph$Subject=="1","Time"]
y = Theoph[Theoph$Subject=="1","conc"]

sNCA(x, y, dose=320, doseUnit="mg", concUnit="mg/L", timeUnit="h")
sNCA(x, y, dose=320, concUnit="mg/L", returnNA=FALSE)

iAUC = data.frame(Name=c("AUC[0-12h]","AUC[0-24h]"), Start=c(0,0), End=c(12,24))
sNCA(x, y, dose=320, doseUnit="mg", concUnit="mg/L", timeUnit="h", iAUC=iAUC)

MW = 180.164 # Molecular weight of theophylline

sNCA(x, y/MW, dose=320, doseUnit="mg", concUnit="mmol/L", timeUnit="h")
sNCA(x, y/MW, dose=320, doseUnit="mg", concUnit="mmol/L", timeUnit="h", MW=MW)
sNCA(x, y, dose=320/MW, doseUnit="mmol", concUnit="mg/L", timeUnit="h", MW=MW)
sNCA(x, y/MW, dose=320/MW, doseUnit="mmol", concUnit="mmol/L", timeUnit="h", MW=MW)

sNCA(x, y/MW, dose=320/MW, doseUnit="mmol", concUnit="mmol/L", timeUnit="h", MW=MW, 
     returnNA=FALSE)
sNCA(x, y/MW, doseUnit="mmol", concUnit="mmol/L", timeUnit="h", MW=MW, returnNA=FALSE)
sNCA(x, y/MW, dose=as.numeric(NA), doseUnit="mmol", concUnit="mmol/L", timeUnit="h", 
     MW=MW, returnNA=FALSE)

sNCA(x, y, dose=320, concUnit="mg/L", timeUnit="hr")
sNCA(x*60, y, dose=320, concUnit="mg/L", timeUnit="min")

Table output NCA

Description

do multiple NCA and returns a result table.

Usage

tblNCA(concData, key = "Subject", colTime = "Time", colConc = "conc", dose = 0, 
       adm = "Extravascular", dur = 0, doseUnit = "mg", timeUnit = "h", 
       concUnit = "ug/L", down = "Linear", MW = 0, returnNA = FALSE)

Arguments

Value

Basically same with sNCA

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, sNCA

Examples

tblNCA(Theoph, key="Subject", dose=320, concUnit="mg/L")
tblNCA(Indometh, key="Subject", colTime="time", colConc="conc", dose=25, 
       adm="Infusion", dur=0.5, concUnit="mg/L")

Text output of NCA for one subject

Description

This is the text form output.

Usage

txtNCA(x, y, dose = 0, adm = "Extravascular", dur = 0, doseUnit = "mg", timeUnit = "h", 
       concUnit = "ug/L", iAUC = "", down="Linear", MW = 0, returnNA = FALSE)

Arguments

Value

Author(s)

Kyun-Seop Bae <k@acr.kr>

See Also

help, pdfNCA, rtfNCA

Examples

# For one subject
txtNCA(Theoph[Theoph$Subject=="1","Time"], Theoph[Theoph$Subject=="1","conc"], 
       dose=320, doseUnit="mg", concUnit="mg/L", timeUnit="h")

# or equivalently
x = Theoph[Theoph$Subject=="1","Time"]
y = Theoph[Theoph$Subject=="1","conc"]
txtNCA(x, y, dose=320, doseUnit="mg", concUnit="mg/L", timeUnit="h")

# For all subjects
IDs = sort(as.numeric(unique(Theoph[,"Subject"])))
nID = length(IDs)
Res = vector()
for (i in 1:nID) {
  tRes = txtNCA(Theoph[Theoph[,"Subject"]==IDs[i],"Time"], 
                Theoph[Theoph[,"Subject"]==IDs[i],"conc"], 
                dose=320, concUnit="mg/L", returnNA=FALSE)
  tRes = c(paste("ID =", IDs[i]), tRes, "")
  Res = c(Res, tRes)
}
Res