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Background: Crohn's disease (CD) is a chronic inflammatory bowel disease that impacts the intestine function; the drug metabolism enzymes and transporters (DMETs) are part of the affected variables. The observed inflammation effect on the enzymes and transporters causes alteration of the intestine absorption and metabolism capacity, hence, oral drug bioavailability. Dosing guidance and regulations for CD population are lacking. Importance of such practice implementation can be carried out via in silico physiologically-based pharmacokinetic (PBPK) modelling. The CD population is a heterogenic population, as different system parameters are altered differently in the active and remission phases of the disease. Methods: Literature gap analysis was performed to collect the available information of system parameters that impact oral drug pharmacokinetics (PK) and identify the gaps hindering appropriate PBPK predictions in CD patients utilising Simcyp simulator. By experimentation, LC-MS/MS-based label free proteomics was carried out to generate in vitro abundance data of DMETs in CD tissue samples. The desired proteins were quantified in 8 and 12 diseased ileum and colon samples respectively, compared to 10 healthy samples. The determined proteins level were integrated into the created CD PBPK models to assess oral drug PK in CD population. Results: The protein abundance of 61 and 48 DMETs in ileum and colon, respectively, decreased in inflamed and histologically normal homogenate samples of CD relative to healthy samples. The reduction of cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) and non-CYP non-UGT enzymes, ATP-binding cassette (ABC) transporters and Solute Carriers (SLC) abundance in the tissues derived from CD subjects were comparable with varying levels of significance. Abundance values of proteins relevant to budesonide and midazolam were used in the created PBPK models of CD population to validate their predictive performance. Moreover, the PBPK models were used to investigate the PK profile of 10 oral drugs, where celecoxib, dabigatran etexilate, gemfibrozil, ritonavir, valsartan and verapamil demonstrated >2 fold change in their exposure in CD compared with healthy population. Conclusion: To our knowledge, the work carried out in this thesis provides for the first time, direct protein abundance data of DMETs in histologically normal and inflamed ileum and colon tissues from individual CD patients. This proteomics data supports the development of CD PBPK models, which highlight the importance of using special population data to aid in guiding dose adjustments.