Evaluation of an In Silico PBPK Postbariatric Surgery Model through Simulating Oral Drug Bioavailability of Atorvastatin and Cyclosporine

An increasing prevalence of morbid obesity has led to dramatic increases in the number of bariatric surgeries performed. Altered gastrointestinal physiology following surgery can be associated with modified oral drug bioavailability (F_oral). In the absence of clinical data, an indication of changes to F_oral via systems pharmacology models would be of value in adjusting dose levels after surgery. A previously developed virtual “post-bariatric surgery” population was evaluated through mimicking clinical investigations on cyclosporine and atorvastatin after bariatric surgery. Cyclosporine simulations displayed a reduced fraction absorbed through gut wall (f_a) and F_oral after surgery, consistent with reported observations. Simulated atorvastatin F_oral postsurgery was broadly reflective of observed data with indications of counteracting interplay between reduced f_a and an increased fraction escaping gut wall metabolism (F_G). Inability to fully recover observed atorvastatin exposure after biliopancreatic diversion with duodenal switch highlights the current gap regarding the knowledge of associated biological changes.