nlmixr2autoinit (version 1.0.0)

ka_calculation_md: Calculate absorption rate constant (ka) in a multiple-dose one-compartment model

Description

This estimates the absorption rate constant in a multiple-dose oral model using first-order pharmacokinetics.

Usage

ka_calculation_md(cl, ke, t, Ct, Fbio = 1, Dose, tau)

Value

A list containing the following components:

ka

The calculated absorption rate constant.

full_solution

The full solution object returned by the uniroot() function, which includes additional details about the root-finding process.

Arguments

cl

Numeric. Clearance of the drug (in L/hr).

ke

Numeric. Elimination rate constant (in 1/hr).

t

Numeric. Time after the last dose (in hours) at which the concentration is measured.

Ct

Numeric. Observed concentration of the drug at time t (in mg/L).

Fbio

Numeric. Bioavailability fraction (default = 1, meaning 100% bioavailability).

Dose

Numeric. Administered dose of the drug (in mg).

tau

Numeric. Dosing interval (in hours) between successive doses.

Author

Zhonghui Huang

Details

The value of ka is obtained numerically using the uniroot unction by solving the following equation:

$$Ct = \frac{Fbio \cdot Dose \cdot ka}{Vd \cdot (ka - ke)} \left( \frac{e^{-ke \cdot t}}{1 - e^{-ke \cdot \tau}} - \frac{e^{-ka \cdot t}}{1 - e^{-ka \cdot \tau}} \right)$$

ka is estimated using uniroot(), which solves for the root of the residual function (predicted Ct - observed Ct) within a bounded interval (ka > ke and ka <= 1000)

Examples

# Example from Oral_1CPT dataset (ID = 1, 5th dose, t = 2 h)
ka_calculation_md(cl = 4, ke = 0.057, t = 2, Ct = 852, Dose = 60000, tau = 24)