Update on the Pharmacogenomics of Proton Pump Inhibitors

Krisztina Hagymási; Katalin Müllner; László Herszényi; Zsolt Tulassay


Pharmacogenomics. 2011;12(6):873-888. 

In This Article

Pharmacokinetic Properties of PPIs

Proton pump inhibitors pass through the stomach intact and are absorbed in the proximal small bowel. All the products achieve peak concentrations of approximately 0.5 to 2 mg/ml. Once absorbed, all PPIs have a relatively short plasma half-life (~1–2 h). All of the PPIs undergo low rates of hepatic first-pass metabolism. The oral bioavailability of PPIs is high: 77% for pantoprazole, 80–90% for lansoprazole and 89% for esomeprazole.[4] In addition, protein binding of all the PPI's is 95% or greater.[5] All of the PPI's are extensively metabolized in the liver to inactive metabolites (see 'Metabolism of PPIs' section). All of the PPI's undergo elimination in urine and feces and have elimination half-lives of 1.5 h or less. All of the drugs are cleared mainly as metabolites owing to their high degree of metabolism (Table 1).

While the half-life time of PPIs is rather similar, differences in the maximal plasma concentrations (Cmax) and in the area under curve (AUC; total area under the plasma drug concentration–time curve), values are more pronounced.[6]

The area under the plasma concentration-time curve increases in a nonlinear fashion at repeated doses of omeprazole and esomeprazole. By contrast, there is a linear correlation between Cmax and AUC0–24 values after repeated application of lansoprazole, pantoprazole and rabeprazole. These differences in the cases of omeprazole and esomeprazole compared with other PPIs are the result of their significant inhibition of the cytochrome P450 (CYP) isoenzyme (CYP2C19), which is mainly responsible for their metabolic clearance. A similar phenomenon has not been discovered in the pharmacokinetics of lansoprazole, pantoprazole and rabeprazole.[6]


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