The pKa (the pH at which 50% of the drug becomes positively charged) of rabeprazole is around 5.0, meaning that it doesnt take a lot of acid to activate it. While this theoretically translates into a faster onset of action for rabeprazoles acid-inhibiting effect, the clinical implications of this fact have yet to be elucidated. Pharmacokinetics
Rabeprazoles bioavailability is approximately 52%, meaning that 52% of orally administered dose is expected to enter systemic circulation (the bloodstream). Once in the blood, rabeprazole is approximately 96.3%-97% bound to plasma proteins. The biological half-life of rabeprazole in humans is approximately one hour. It takes about 3.5 hours for rabeprazole to reach the maximum concentration in human plasma after a single orally administered dose. Oral absorption is independent of the dose administered.Rabeprazole is extensively metabolized by the liver. 90% of the drug is rendered into metabolites by the liver, which are then excreted by the kidneys. 10% of the dose is excreted in the feces. The drug metabolizing enzymes primarily responsible for rabeprazoles metabolism are CYP2C19 and CYP3A4. However, rabeprazole is mainly metabolized through non-enzymatic reduction to a thioether metabolite. Some of rabeprazoles metabolites include the following: a thioether carboxylic acid metabolite, a thioether glucuronide metabolite, and a sulfone metabolite. The most common metabolites excreted in the urine are the mercapturic acid conjugate and carboxylic acid. A diagram of rabeprazoles phase I metabolism is shown below. Pharmacogenetics
The effect of rabeprazole may vary based upon the genetics of the individual taking the medication.
Rare instances of rabeprazole-induced liver injury (also known as hepatotoxicity) have been reported. Characteristic proton-pump inhibitor hepatoxicity usually occurs within the first four weeks of starting the medication.Rabeprazole is associated with elevated serum gastrin levels, which are thought to be dependent upon the degree of CYP2C19 metabolism the drug undergoes. In comparison, rabeprazole is not as significantly metabolized by this enzyme compared to other medications in the same class, like omeprazole. Elevated serum gastrin may be associated with gastric cancer.Acid suppression via rabeprazole can decrease the absorption of vitamin B12 and magnesium, leading to deficiency.Very serious side effects have been reported in people taking rabeprazole, but these effects have not been "correlated directly" with the use of rabeprazole. These include Stevens–Johnson syndrome, serious hematological abnormalities, coma, and death. Other possible side effects, common to other PPIs medications in the same class, include bone fractures due to osteoporosis and serious infections with Clostridium difficile. Overdose
No signs and symptoms have been reported in overdoses of rabeprazole up to 80 mg, but case examples are limited. Notably, rabeprazole has been used in higher doses for the treatment of hypersecretory conditions like Zollinger-Ellison syndrome (up to 120 mg daily).Animal experiments with ultra-high doses of rabeprazole have demonstrated lethality through unknown mechanisms. The lethal overdose syndrome in animals is characterized by convulsion and coma. Interactions
Drug-drug interactions
Rabeprazole does not interfere with the plasma concentration of drugs that are also metabolized by the same enzymes (i.e. CYP2C19) that it is metabolized by.