Prediction of Therapeutic Doses Based on the Pharmacokinetic/Pharmacodynamic Model of Omeprazole, a Proton Pump Inhibitor

Abstract

The pharmacokinetic/pharmacodynamic model considering the effect of omeprazole, an anti-ulcer drug, on the metabolic turn-over of H⁺/K⁺ ATPase (proton pump) was developed. The pharmacokinetic and pharmacodynamic parameters of omeprazole were calculated based on the plasma concentration profile and the inhibition ratio of gastric acid secretion after single oral administration of omeprazole at the dose of 40mg.
Reaction rate constant of omeprazole with proton pump and the elimination rate constant of PP were 1.2 M^-1·hr^-1 and 0.0243hr-¹, respectively. Simulation profiles of inhibition ratio of gastric acid secretion after single and repeated oral administration of omeprazole are consistent with the data reported by other investigators. Dose-response curve shifted to a lower dose after repeated administration of omeprazole, as compared with that after single administration. The correlation between the clearance of metabolic turn-over of proton pump and the body weight seems to follow Adolph's power law, suggesting the possibility of prediction of human's therapeutic dose of omeprazole from animal data.