Calculate derived pharmacokinetic parameters for a 1-, 2-, or 3-compartment linear model.

Usage

calc_derived(..., verbose = FALSE)

calc_derived_1cpt(
  CL,
  V = NULL,
  V1 = NULL,
  ka = NULL,
  dur = NULL,
  tlag = NULL,
  tinf = NULL,
  dose = NULL,
  tau = NULL,
  step = 0.1,
  type = "all",
  sigdig = 5
)

calc_derived_2cpt(
  CL,
  V1 = NULL,
  V2,
  Q2 = NULL,
  V = NULL,
  Q = NULL,
  dur = NULL,
  tinf = NULL,
  ka = NULL,
  tlag = NULL,
  dose = NULL,
  tau = NULL,
  step = 0.1,
  type = "all",
  sigdig = 5
)

calc_derived_3cpt(
  CL,
  V1 = NULL,
  V2,
  V3,
  Q2 = NULL,
  Q3,
  V = NULL,
  Q = NULL,
  ka = NULL,
  dur = NULL,
  tinf = NULL,
  tlag = NULL,
  dose = NULL,
  tau = NULL,
  step = 0.1,
  type = "all",
  sigdig = 5
)

Arguments

...: Passed to the other calc_derived_*() functions.
verbose: For calc_derived(), provide a message indicating the type of model detected.
CL: Clearance (volume per time units, e.g. L/h)
V1, V: Central volume of distribution (volume units, e.g. L). Values are synonyms; use only one.
ka: Absorption rate (inverse time units, e.g. 1/h)
dur: Duration of zero-order absorption (time units, e.g. h)
tlag: Absorption lag time (time units, e.g. h)
tinf: Duration of infusion (time units, e.g. h)
dose: Dose (amount units, e.g. mg)
tau: Duration of interdose interval (time units, e.g. h; defaults to 24)
step: Time increment to use when estimating NCA parameters (time units, e.g. h; defaults to 0.1)
type: Parameters to return. Default is "all". If not "all", this may be a vector from the names of the return value list.
sigdig: Number of significant digits to be returned. Default is 5.
V2: First peripheral volume of distribution (volume units, e.g. L)
Q2, Q: Intercompartmental clearance from central to first peripheral compartment (volume per time units, e.g. L/h). Values are synonyms; use only one.
V3: Second peripheral volume of distribution (volume units, e.g. L)
Q3: Intercompartmental clearance from central to second peripheral compartment (volume per time units, e.g. L/h)

Value

Return a list of derived PK parameters for a 1-, 2-, or 3-compartment linear model given provided clearances and volumes based on the type. If a dose is provided, estimated non-compartmental analysis (NCA) parameters will be provided as well, based on simulation of single-dose and (if `tau` is specified) steady-state time courses.

Vss: Volume of distribution at steady state, \(V_{ss}\) (volume units, e.g. L); 1-, 2-, and 3-compartment
k10: First-order elimination rate, \(k_{10}\) (inverse time units, e.g. 1/h); 1-, 2-, and 3-compartment
k12: First-order rate of transfer from central to first peripheral compartment, \(k_{12}\) (inverse time units, e.g. 1/h); 2- and 3-compartment
k21: First-order rate of transfer from first peripheral to central compartment, \(k_{21}\) (inverse time units, e.g. 1/h); 2- and 3-compartment
k13: First-order rate of transfer from central to second peripheral compartment, \(k_{13}\) (inverse time units, e.g. 1/h); 3-compartment
k31: First-order rate of transfer from second peripheral to central compartment,\(k_{31}\) (inverse time units, e.g. 1/h); 3-compartment
thalf_alpha: \(t_{1/2,\alpha}\) (time units, e.g. h); 1-, 2-, and 3-compartment
thalf_beta: \(t_{1/2,\beta}\) (time units, e.g. h); 2- and 3-compartment
thalf_gamma: \(t_{1/2,\gamma}\) (time units, e.g. h); 3-compartment
alpha: \(\alpha\); 1-, 2-, and 3-compartment
beta: \(\beta\); 2- and 3-compartment
gamma: \(\beta\); 3-compartment
trueA: true A; 1-, 2-, and 3-compartment
trueB: true B; 2- and 3-compartment
trueC: true C; 3-compartment
fracA: fractional A; 1-, 2-, and 3-compartment
fracB: fractional B; 2- and 3-compartment
fracC: fractional C; 3-compartment
AUCinf: Area under the concentration-time curve to infinity (single dose)
AUCtau: Area under the concentration-time curve over the dosing interval at steady state
Cmax: Maximum concentration after a single dose
Cmaxss: Maximum concentration over the dosing interval at steady state
Tmax: Time after dose of maximum concentration
AUCinf_dose_normalized: Dose-normalized area under the concentration-time curve to infinity (single dose)
AUCtau_dose_normalized: Dose-normalized area under the concentration-time curve over the dosing interval at steady state
Cmax_dose_normalized: Dose-normalized maximum concentration after a single dose
Cmaxss_dose_normalized: Dose-normalized maximum concentration over the dosing interval at steady state
step: Time increment used when estimating NCA parameters.

The input parameters with standardized names (dose, V1, V2, V3, CL, Q2, and Q3) are also returned in the list, and if provided, additional PK parameters of `ka`, `tlag`, `tinf` and `dur` are also returned in the list. All inputs may be scalars or vectors.

References

Shafer S. L. CONVERT.XLS

Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications (4th). Lippincott Williams & Wilkins, Philadelphia, 2010.

Author

Justin Wilkins, justin.wilkins@occams.com

Bill Denney, wdenney@humanpredictions.com

Examples

params <- calc_derived(CL=29.4, V1=23.4, V2=114, V3=4614, Q2=270, Q3=73)
params <- calc_derived_1cpt(CL=16, V=25)
params <- calc_derived_2cpt(CL=16, V1=25, V2=50, Q=0.5)
params <- calc_derived_3cpt(CL=29.4, V1=23.4, V2=114, V3=4614, Q2=270, Q3=73)