calc_derived function

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

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)

Returns

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.

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)

References

Shafer S. L. CONVERT.XLS

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

Author(s)

Justin Wilkins, justin.wilkins@occams.com

Bill Denney, wdenney@humanpredictions.com