Proton pump inhibitors half-life

Indications Gastroesophageal Reflux Disease (GERD) Category Proton pump inhibitor Half-life 1.5 hours... 

Category Proton pump inhibitor Half-life I hour... 

From a pharmacokinetic perspective, proton pump inhibitors are ideal drugs they have a short serum half-life, they are concentrated and activated near their site of action, and they have a long duration of action. 

The pharmacokinetics of available proton pump inhibitors are shown in Table 63-2. Their bioavailability is decreased approximately 50% by food hence, the drugs should be administered on an empty stomach. In a fasting state, only 10% of proton pumps are actively secreting acid and susceptible to inhibition. Proton pump inhibitors should be administered approximately 1 hour before a meal (usually breakfast or dinner), so that the peak serum concentration coincides with the maximal activity of proton pump secretion. The drugs have a short serum half-life of about 1.5 hours however, the duration of acid inhibition lasts up to 24 hours due to the irreversible inactivation of the proton pump. At least 18 hours are required for synthesis of new H+/K+ ATPase pump molecules. Because not all proton pumps are inactivated with the first dose of medication, up to 3-4 days of daily medication are required before the full acid-inhibiting potential is reached. Similarly, after stopping the drug, it takes 3-4 days for full acid secretion to return. 

From a pharmacokinetic perspective, proton pump inhibitors are ideal drugs they have a short serum half-life, they are concentrated and activated near their site of action, and they have a long duration of action. In contrast to H2 antagonists, proton pump inhibitors inhibit both fasting and meal-stimulated secretion because they block the final common pathway of acid secretion, the proton pump. In standard doses, proton pump inhibitors inhibit 90-98% of 24-hour acid secretion. 

Esomeprazole is the 5-isomer of omeprazole. The pharmacology, pharmacokinetics, efficacy, and safety of esomeprazole have been reviewed (1). Esomeprazole produces acid control comparable to that of currently available proton pump inhibitors. It undergoes less hepatic metabolism than omeprazole, has an oral availability of 89% at a dose of 40 mg, and a half-life of 1.5 hours. Esomeprazole is well tolerated its common adverse effects are diarrhea, headache, nausea, abdominal pain, respiratory infection, and sinusitis. 

Ketoconazole is water-soluble at a pH of below 3. Its oral absorption is influenced by the acidity of the stomach contents, and the concomitant administration of histamine H2 receptor antagonists, proton pump inhibitors, antacids, or food affects its absorption. A high carbohydrate meal ingested with ketoconazole reduces total drug absorption, while a high lipid meal increases it. Erratic absorption is particularly apparent in patients with AIDS. Peak serum concentrations are seen within 2-3 hours. The half-life is about 8 hours. CSF penetration is less than 10% (1). Ketoconazole is extensively metabolized in the liver and excreted in the bile in an inactive form less than 1% of the active drug is excreted in the urine. Clearance is not significantly altered by renal dialysis (1). 

CYP2C19 metabolizes many clinically important drugs (Table 12.3). Subjects with the CYP2C19 PM phenotype have an area under the curve (AUC) of omeprazole that is more than sixfold higher than efficient metabolizers (EM), and the drug has a severely prolonged half-life in PM individuals (48). A similar relationship is seen for other proton pump inhibitors (49). To reach similar plasma levels, PMs of CYP2C19 would take about 1-2 mg of omeprazole instead of the recommended dose of 20 mg (50). 

Prilosec, Rapinex, Zegerid) and its S-isomer, esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix). These drugs have different substitutions on their pyridine and/or benzimidazole groups but are remarkably similar in their pharmacological properties. Omeprazole is a racemic mixture of R- and S-isomers the S-isomer, esomeprazole (S-omeprazole), is eliminated less rapidly than R-omeprazole, which theoretically provides a therapeutic advantage because of the increased half-life. Despite claims to the contrary, all proton-pump inhibitors have equivalent efficacy at comparable doses. 

Proton pump inhibitors (PPIs) such as omeprazole, lanzoprazole and pan-toprazole are chemically characterized as substituted benzimidazoles. They are chemically relatively stable at neutral pH tia = 24 h), whereas at acidic pH they are labile and at pH 1 the half-life is 2 min. 

The half-life of the a subunit has usually been inferred rather than directly measured. Thus, treatment of rats with cycloheximide resulted in a loss of ATPase activity with a half-life of 72 h [29]. Recovery from inhibition with the covalent inhibitor, omeprazole, showed a half-life of 30 h in the same series of experiments. Other workers have claimed a half-life of recovery from proton pump inhibition of as short as 15 h [30]. 

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