nca.bioavailability¶

Absolute and relative bioavailability from two non-compartmental analyses.

The fraction of a dose which reaches the systemic circulation is not measured directly: it is the exposure of the test treatment against the exposure of a reference treatment, both divided by their dose,

\[F = \frac{\mathrm{AUC}_\mathrm{test} / D_\mathrm{test}} {\mathrm{AUC}_\mathrm{ref} / D_\mathrm{ref}}.\]

With an intravenous reference, whose fraction absorbed is 1 by definition, this is the absolute bioavailability \(F_\mathrm{abs}\) (CDISC FABS); with any other reference - another formulation, another route, a fed against a fasted state - it is the relative bioavailability \(F_\mathrm{rel}\) (CDISC FREL). The FDA bioavailability guidance asks for exactly this comparison, and PKNCA computes it as pk.calc.f.

bioavailability is the geometric mean ratio of the dose normalized exposures with its confidence interval, the same estimator a bioequivalence study uses (pkpdutils.stats.ratio): the exposures are log-normal, the subjects of a crossover are paired and the interval is a t interval on the log scale.

is_intravenous ¶

is_intravenous(result)

Whether a result comes from an intravenous analysis.

A result which names the route of its batch (attrs["route"], or the coordinate route when every sample was given the same one) is read there. Otherwise the variables the route decides answer it: an intravenous analysis reports cl, vz and vss (and c0 after a bolus) where an extravascular one reports cl_f and vz_f.

Parameters:

Name	Type	Description	Default
`result`	`NCAResult`	the result	required

Returns:

Type	Description
`bool`	`True` for an intravenous route, or when the result carries an
`bool`	intravenous variable and no extravascular one.

bioavailability ¶

bioavailability(
    test,
    reference,
    *,
    dim,
    parameter="auc_inf_obs",
    paired=None,
    ci_level=0.9,
    reference_route=None,
)

Absolute or relative bioavailability of a test against a reference analysis.

The dose normalized exposure of every subject (NCAResult.dose_normalized, \(x / D\)) of both results is compared as a geometric mean ratio with its confidence interval (pkpdutils.stats.ratio),

\[F = \frac{\mathrm{AUC}_\mathrm{test} / D_\mathrm{test}} {\mathrm{AUC}_\mathrm{ref} / D_\mathrm{ref}},\]

paired by the label of dim when both results carry the same subjects (a crossover) and unpaired otherwise (a parallel design, the Welch interval). The name of the result says which quantity it is: f_abs with an intravenous reference, whose fraction absorbed is 1, and f_rel with any other one.

Parameters:

Name	Type	Description	Default
`test`	`NCAResult`	the analysis of the test treatment	required
`reference`	`NCAResult`	the analysis of the reference treatment	required

Other Parameters:

Name	Type	Description
`dim`	`str`	the sample dimension of the subjects of both results
`parameter`	`str`	the exposure to compare, `auc_inf_obs` by default; `auc_last` and `auc_tau` are the other usual choices
`paired`	`bool \| None`	pair the subjects by label; `None` pairs when both results carry the same labels (`pkpdutils.stats.ratio`)
`ci_level`	`float`	level of the interval, 0.90 as in bioequivalence
`reference_route`	`Route \| None`	the route of the reference treatment; `None` reads it off the variables of the reference result (`is_intravenous`)

Returns:

Type	Description
`RatioResult`	The ratio, named `f_abs` or `f_rel`, with the unit `dimensionless`:
`RatioResult`	the exposures are divided by their dose before they are compared.

Raises:

Type	Description
`ValueError`	if a result carries no dose (`NCAResult.dose_normalized`), if `parameter` is not a parameter of both results or if `dim` is not a sample dimension of both.