Contents

The structure of the current compartments used for model simulation is presented in the figure below:

PBPK model

The current model has a few assumptions and limitations*:

  1. The oral model assumes that all the drug in the stomach is in the dissolved form and in fasted state.
  2. There is no reabsorption from the large intestine.
  3. The distribution model is blood flow limited.
  4. The organs/tissue compartments have instantaneous uniform drug distribution across.
  5. The drug release from the intramuscular and subcutaneous depot sites are of the first order.
  6. Teoreler currently has three PBPK models - Human adult (18-60 years) model, a rat model and a mouse model. Currently these models are suitable for simulating drugs that are not induced or inhibited by any en

* - the model would be updated in the future to address the current limitations.

Population

The population characteristics used in the model are obtained from NHANES datasets from various years ranging from 1976 - 2018.3 The age, weight and height of the individual are generated randomly. Based on the weight and height, BMI and BSA are computed. If the BMI is not in the acceptable range (i.e. <65 kg/m² for males, and <80 kg/m² for females, according to the NHAHES dataset), a new individual is generated until it satisfies that condition.

Organs and Tissues

The organ weights were computed using various anthropometric equations obtained from the literature.4The organ weights depend on the population characteristics - age, weight, height, bmi and bsa of the individual.
The organ volumes were computed using the organ weights and organ densities.

Blood flow

The cardiac output (Qco) was computed from the weight of the individual5as represented by the following equation:
Qco= 15 × (BW) 0.74[ 1 ]
The blood flow rate to the individual organs was computed as a percentage of the cardiac output.5

Absorption

The small intestine has been divided into seven different compartments.6 The parameters for the transit rates across the gastrointestinal tract (GIT) mimic the fasted state of a human. Drug transition and absorption occurs simultaneously across the seven compartements of the small intestine.