*2.7. Pharmacokinetic Modeling*

Pharmacokinetic modeling of the plasma concentration-time profile of tadalafil was performed using a one-compartment model to investigate the absorption and elimination rates. The parameters of the one-compartment model of tadalafil were estimated based on data from Group N and Group T.

In this model, the shift of the tadalafil amount in the gu<sup>t</sup> compartment and the central compartment is described by the following equations [33]:

$$\frac{dG}{dt} = -K\_{\text{fl}} \cdot G$$

$$\frac{d\mathbf{C}}{dt} = K\_{\text{fl}} \cdot G - K\_{\text{f}} \cdot \mathbf{C}$$

where *G* and *C* represent the amount of tadalafil in the gu<sup>t</sup> compartment and the central compartment, respectively. *Ka* indicates the absorption rate constant from the gu<sup>t</sup> compartment to the central compartment. *Ke* indicates the elimination rate constant from the central compartment to the gu<sup>t</sup> compartment. Each equation was applied to both Group N and Group T data through the classic model of WinNolin software 8.1 (Pharsight Corp., Sunnyvale, CA, USA).

Predicted plasma concentrations of tadalafil (*Conpred*) using the one-compartment model were estimated by the following equation [34]:

$$Con\_{pred} = \text{C} / (V/F)$$

where *V*/*F* indicates the central volume of distribution of tadalafil.

The fold error versus concentration or time was calculated using the following equation [35]:

$$Fold\,error = \frac{Con\_{pred} - Con\_{obs}}{Con\_{obs}}$$

where *Conpred* indicates the predicted concentration of tadalafil from the one-compartment pharmacokinetic modeling and *Conobs* indicates the observed concentration of tadalafil from the pharmacokinetic experiment. The fold error within ±2-fold is an acceptable range [35].
