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Estimate the optimal dosing interval to consistently achieve a target trough concentration (Cmin)

Source: R/dosing_optim.R
poso_inter_cmin.Rd

Estimates the optimal dosing interval to consistently achieve a target Cmin, given a dose, a population pharmacokinetic model, a set of individual parameters, and a target concentration.

Usage

poso_inter_cmin(
  dat = NULL,
  prior_model = NULL,
  dose,
  target_cmin,
  cmt_dose = 1,
  endpoint = "Cc",
  estim_method = "map",
  nocb = FALSE,
  p = NULL,
  greater_than = TRUE,
  starting_interval = 12,
  add_dose = 10,
  duration = 0,
  indiv_param = NULL
)

Arguments

dat

Dataframe. An individual subject dataset following the structure of NONMEM/rxode2 event records.

prior_model

A posologyr prior population pharmacokinetics model, a list of six objects.

dose

Numeric. The dose given.

target_cmin

Numeric. Target trough concentration (Cmin).

cmt_dose

Character or numeric. The compartment in which the dose is to be administered. Must match one of the compartments in the prior model. Defaults to 1.

endpoint

Character. The endpoint of the prior model to be optimised for. The default is "Cc", which is the central concentration.

estim_method

A character string. An estimation method to be used for the individual parameters. The default method "map" is the Maximum A Posteriori estimation, the method "prior" simulates from the prior population model, and "sir" uses the Sequential Importance Resampling algorithm to estimate the a posteriori distribution of the individual parameters. This argument is ignored if indiv_param is provided.

nocb

A boolean. for time-varying covariates: the next observation carried backward (nocb) interpolation style, similar to NONMEM. If FALSE, the last observation carried forward (locf) style will be used. Defaults to FALSE.

p

Numeric. The proportion of the distribution of concentrations to consider for the optimization. Mandatory for estim_method=sir.

greater_than

A boolean. If TRUE: targets a dose leading to a proportion p of the concentrations to be greater than target_conc. Respectively, lower if FALSE.

starting_interval

Numeric. Starting inter-dose interval for the optimization algorithm.

add_dose

Numeric. Additional doses administered at inter-dose interval after the first dose.

duration

Numeric. Duration of infusion, for zero-order administrations.

indiv_param

Optional. A set of individual parameters : THETA, estimates of ETA, and covariates.

Value

A list containing the following components:

interval

Numeric. An inter-dose interval to reach the target trough concentration before each dosing of a multiple dose regimen.

type_of_estimate

Character string. The type of estimate of the individual parameters. Either a point estimate, or a distribution.

conc_estimate

A vector of numeric estimates of the conc. Either a single value (for a point estimate of ETA), or a distribution.

indiv_param

A data.frame. The set of individual parameters used for the determination of the optimal dose : THETA, estimates of ETA, and covariates

Examples

rxode2::setRxThreads(2L) # limit the number of threads