Predicting Efficacy of Proton Pump Inhibitors in Regulating Gastric Acid Secretion

Developing drugs to treat gastric acid related illnesses such as ulcers and acid reflux disease is the leading focus of pharmaceutical companies. In fact, expenditure for treating these disorders is highest among all illnesses in the US. Over the last few decades, a class of drugs known as a proton pump inhibitors (PPIs) appeared on the market and are highly effective at abating gastric illnesses by raising stomach pH (reducing gastric acid levels). While much is known about the action of PPIs, there are still open questions regarding their efficacy, dosing and long-term effects. Here we extend a previous gastric acid secretion model developed by our group to incorporate a pharmacodynamic/pharmacokinetic model to study proton pump inhibitor (PPI) action. Modelrelevant parameters for specific drugs such as omeprazole (OPZ), lansoprazole (LPZ) and pantoprazole (PPZ) were used from published data, and we conducted simulations to study various aspects of PPI treatment. Clinical data suggests that duration of acid suppression is dependent on proton pump turnover rates and this is supported by our model. We found the order of efficacy of the different PPIs to be OPZ > PPZ > LPZ for clinically recommended dose values, and OPZ > PPZ = LPZ for equal doses. Our results indicate that a breakfast dose for once-daily dosing regimens and a breakfastlunch dose for twice-daily dosing regimens is recommended. Simulation of other gastric disorders using our model provides atypical applications for the study of drug treatment on homeostatic systems and identification of potential side-effects.