Omeprazole pharmacokinetics
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Omeprazole Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion
Absorption and Bioavailability of Omeprazole
Omeprazole is acid-labile, so oral formulations are designed to protect it from stomach acid. When given as a buffered suspension, omeprazole is rapidly absorbed, reaching peak plasma concentrations within 0.5 hours. However, when administered as enteric-coated granules, absorption is slower, with peak concentrations occurring 1–3 hours after dosing. The bioavailability after a single dose is about 35%, but this increases to 60% with repeated daily dosing due to reduced first-pass metabolism and decreased gastric acidity from the drug’s own effect 167.
Distribution and Elimination
The volume of distribution for omeprazole is about 0.3 L/kg, similar to the volume of extracellular water. Omeprazole is rapidly eliminated from plasma, with a half-life of less than 1 hour, and is almost entirely cleared from plasma within 3–4 hours . Despite this rapid elimination, its antisecretory effect lasts much longer due to its mechanism of action on gastric proton pumps .
Metabolism and Excretion
Omeprazole is completely metabolized in the liver, primarily by the cytochrome P450 enzymes CYP2C19 and CYP3A4. The main plasma metabolites are omeprazole sulphone and hydroxyomeprazole, which do not contribute to its acid-suppressing effects. About 80% of a dose is excreted in the urine, with the remainder eliminated via bile .
Influence of Genetics and Disease States
Genetic differences, especially in the CYP2C19 enzyme, significantly affect omeprazole metabolism. Individuals with the CYP2C19*17 allele metabolize omeprazole faster, resulting in lower drug exposure and potentially reduced therapeutic effect . In contrast, conditions like liver cirrhosis or ulcerative colitis reduce the activity of metabolizing enzymes (CYP1A2, CYP3A1), leading to higher plasma concentrations and slower clearance of omeprazole 810.
Pharmacokinetics in Special Populations
- Children: Children, especially those aged 1–6 years, have higher metabolic capacity for omeprazole, resulting in lower plasma levels and a need for higher doses per kilogram compared to adults .
- Obesity and Gastric Bypass: Obesity reduces CYP2C19 and CYP3A4 activity, decreasing omeprazole metabolism. After gastric bypass surgery, enzyme activity is restored, and omeprazole exposure changes accordingly. These factors also influence intragastric pH control .
Drug Interactions and Other Influences
Omeprazole can inhibit hepatic CYP enzymes, decreasing the clearance and increasing the half-life of drugs like diazepam and phenytoin, but not propranolol or theophylline . Co-administration with substances like astragaloside IV can decrease omeprazole exposure by increasing its metabolism and reducing absorption, likely through induction of P-glycoprotein and CYP3A4 .
Central Nervous System and Biliary Excretion
Omeprazole can cross the blood-brain barrier, though at low levels compared to blood, and is also excreted into bile, indicating rapid distribution and equilibration between compartments .
Conclusion
Omeprazole’s pharmacokinetics are influenced by its acid-labile nature, formulation, genetic factors, age, disease states, and drug interactions. It is rapidly absorbed and eliminated, extensively metabolized in the liver, and its exposure can vary widely between individuals and clinical situations. Understanding these factors is crucial for optimizing omeprazole therapy in diverse patient populations.
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