2.5 Estimating drug efficacy-specific parameters in the PK–PD model
An unknown parameter, the extraction ratio in the liver part E , in the PK–PD model must be experimentaly estimated using the MO–MPS. Drug efficacy tests using two different types of the MO–MPS with different flow rates in the liver part were carried out. CPT-11 (2688, Tocris Bioscience, UK), an anticancer drug widely used in the treatment of alveolus and large intestine cancers, was used as a drug model. Two types of the MO–MPS with and without the bypass channel that have 1:3.3 physiological flow ratio (liver:lung cancer part) and 1:1 non-physiological flow ratio (liver:lung cancer part), respectively, were used to evaluate how flow ratio influences drug efficacy on the MO–MPS. The cells were exposed to 15 µm CPT-11 dissolved in the culture medium, which was exchanged every 24 h. After exposure for 72 h, the cells were stained by hoechst33342 (346-07951, Dojindo Laboratories, Japan) and observed using a CCD camera (DP72, Olympus Corporation, Japan) installed with a fluorescence microscope. The drug effect was evaluated using the density of the A549 cells measured from the fluorescent images. The extraction ratios in the liver part of CPT-11 and SN-38 in the MO–MPS were estimated from the experimental results using the MO–MPS with and without bypass channels and our PK–PD model using Eq. (8).