Get parameters for 2-compartment model and determine whether each is to be estimated from the data
get_params_2comp(
data,
lower_bound = ggplot2::aes(kelim = log(2)/(2 * max(Time_trans)), k12 = log(2)/(2 *
max(Time_trans)), k21 = log(2)/(2 * max(Time_trans)), V1 = 0.01, Fgutabs = 0, kgutabs
= log(2)/(2 * max(Time_trans)), Fgutabs_V1 = 0.01, Rblood2plasma = 0.01),
upper_bound = ggplot2::aes(kelim = log(2)/(0.5 * min(Time_trans[Time_trans > 0])), k12
= log(2)/(0.5 * min(Time_trans[Time_trans > 0])), k21 = log(2)/(0.5 *
min(Time_trans[Time_trans > 0])), V1 = 100, Fgutabs = 1, kgutabs = log(2)/(0.5 *
min(Time_trans[Time_trans > 0])), Fgutabs_V1 = 100, Rblood2plasma = 100),
param_units = ggplot2::aes(kelim = paste0("1/", unique(Time_trans.Units)), V1 =
paste0("(", unique(Dose.Units), ")", "/", "(", unique(Conc.Units), ")"), k21 =
paste0("1/", unique(Time_trans.Units)), k12 = paste0("1/", unique(Time_trans.Units)),
Fgutabs = "unitless fraction", kgutabs = paste0("1/", unique(Time_trans.Units)),
Fgutabs_V1 = paste0("(", unique(Conc.Units), ")", "/", "(", unique(Dose.Units), ")"),
Rblood2plasma = "unitless ratio")
)A `data.frame`with the following variables: - `param_name`: Character: Names of the model parameters - `param_units`: Character: Units of the model parameters - `optimize_param`: TRUE if each parameter is to be estimated from the data; FALSE otherwise - `use_param`: TRUE if each parameter is to be used in evaluating the model; FALSE otherwise -`lower_bounds`: Numeric: The lower bounds for each parameter - `upper_bounds`: Numeric: The upper bounds for each parameter - `start`: Numeric: The starting guesses for each parameter
The data set to be fitted (e.g. the result of [preprocess_data()])
A mapping specified using a call to [ggplot2::aes()], giving the lower bounds for each variable, as expressions which may include variables in `data`.
A mapping specified using a call to [ggplot2::aes()], giving the upper bounds for each variable, as expressions which may include variables in `data`.
A mapping specified using a call to [ggplot2::aes()], giving the units for each variable, as expressions which may include variables in `data`.
Caroline Ring
The full set of model parameters for the 2-compartment model includes `V1`, `kelim`, `k12`, `k21`, `kgutabs`,`Fgutabs`, and `Rblood2plasma`. Whether each one can be estimated from the data depends on what routes of administration are included in the data.
## IV data, no oral data
If IV dosing data are available, but no oral dosing data are available, then only the parameters `V1`, `kelim`, `k12`, and `k21` will be estimated from the data. The parameters `kgutabs` and `Fgutabs` cannot be estimated from IV data alone.
## Oral data, no IV data
If oral dosing data are available, but no IV dosing data are available, then the parameters `kelim`, `k12`, `k21`, and `kgutabs` will be estimated from the data. However, the parameters `Fgutabs` and `V1` cannot be identified separately. From oral data alone, only the ratio `Fgutabs/V1` can be identified. This ratio is represented by a single parameter named `Fgutabs_V1`. `Fgutabs` and `V1` will not be optimized, but `Fgutabs_V1` will be optimized, along with `kelim`, `k12`, `k21`, and `kgutabs`.
## Oral data and IV data
If both oral and IV dosing data are available, then `V1`, `kelim`, `k12`, `k21`, `kgutabs`, and `Fgutabs` will all be estimated from the data.
# Blood and plasma data
If both blood and plasma data are available, then `Rblood2plasma` will be estimated from the data.
# Only one of blood or plasma data
If only one of blood or plasma data are available, then `Rblood2plasma` will be held constant at 1, not estimated from the data.
# Default lower and upper bounds for each parameter
## Default lower and upper bounds for time constants `kelim`, `kgutabs`, `k12`, and `k21`.
Default bounds for time constants `kelim` and `kgutabs` are set based on the time scale of the available data.
The lower bounds are based on the assumption that elimination, absorption, and distribution are very slow compared to the time scale of the study. Specifically, the lower bounds assume thatelimination, absorption, and distribution half-lives are twice as long as the duration of the available study data, or `2*max(Time_trans)`. Under this assumption, the corresponding elimination, absorption, and distribution time constants would be `log(2)/(2*max(Time_trans))`. Therefore, the default lower bounds for `kelim`, `kgutabs`, `k12`, and `k21` are `log(2)/(2*max(Time_trans))`.
Upper bounds are based on the opposite assumption: that elimination, absorption, and distribution are very fast compared to the time scale of the study. Specifically, the upper bounds assume that the elimination, absorption, and distribution half-lives are half as long as the time of the first observation after time 0, or `0.5*min(Time_trans[Time_trans>0])`. Under this assumption, the correspondingelimination, absorption, and distribution time constants would be `log(2)/(0.5*min(Time_trans[Time_trans>0]))`. Therefore, the default lower bounds for `kelim`, `kgutabs`, `k12`, and `k21` are `log(2)/(0.5*min(Time_trans[Time_trans>0]))`.
## Default lower and upper bounds for `V1`
By default, the lower bound for `V1` is 0.01, and the upper bound for `V1` is 100. These values were chosen based on professional judgment.
## Default lower and upper bounds for `Fgutabs`
By default, the lower bound for `Fgutabs` is 0.0, and the upper bound for `Fgutabs` is 1. These are simply the bounds of the physically-meaningful range for a fraction.
## Default lower and upper bounds for `Fgutabs_V1`
By default, the lower bound for the ratio `Fgutabs_V1` is 0.01, and the upper bound is 100. These values were chosen based on professional judgment.
## Default lower and upper bounds for `Rblood2plasma`
By default, the lower bound for the blood:plasma partition coefficient `Rblood2plasma` is 0.01, and the upper bound is 100. These values were chosen based on professional judgment.
# Starting values for each parameter
Starting values for each parameter (starting guesses for the numerical optimizer) are derived from the data using [get_starts_2comp()].
If the starting values returned by [get_starts_2comp()] fall outside the bounds for any parameter(s), then the starting value will be reset to a value halfway between the lower and upper bounds for that parameter.
Other 2-compartment model functions:
auc_2comp(),
cp_2comp(),
cp_2comp_dt(),
get_starts_2comp(),
tkstats_2comp(),
transformed_params_2comp()
Other get_params functions:
get_params_1comp(),
get_params_1comp_cl(),
get_params_1comp_fup(),
get_params_flat()
Other built-in model functions:
auc_1comp(),
auc_1comp_cl(),
auc_2comp(),
auc_flat(),
cp_1comp(),
cp_1comp_cl(),
cp_2comp(),
cp_2comp_dt(),
cp_flat(),
get_params_1comp(),
get_params_1comp_cl(),
get_params_1comp_fup(),
get_params_flat(),
get_starts_1comp(),
get_starts_1comp_cl(),
get_starts_1comp_fup(),
get_starts_2comp(),
get_starts_flat(),
tkstats_2comp(),
transformed_params_2comp()