Description
OMEPRAZOLE BELONGS TO GROUP OF DRUGS CALLED PROTON PUMP INHIBITORS. IT DECREASES THE AMOUNT OF ACID PRODUCED IN THE STOMACH.
THIS COMPOUND BELONGS TO THE CLASS OF ORGANIC COMPOUNDS KNOWN AS SULFINYLBENZIMIDAZOLES. THESE ARE POLYCYCLIC AROMATIC COMPOUNDS CONTAINING A SULFINYL GROUP ATTACHED AT THE POSITION 2 OF A BENZIMIDAZOLE MOIETY.
PHARMACOLOGY
A.)PHARMACODYNAMICS:
After oral administration, the onset of the anti-secretory effect of omeprazole occurs within one hour and maximum effect occurring within two hours. At 24 hours, inhibition of secretion is approximately 50% of maximum and duration of inhibition lasts up to 72 hours. Although omeprazole has a very short plasma half-life, the anti-secretory effect lasts for a long time due to prolonged binding to parietal H+/K+ ATPase enzyme. When the drug has been discontinued, secretory activity will return to baseline over 3-5 days. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days. In studies involving more than 200 patients, serum gastrin levels increased during the first 1 to 2 weeks of once-daily administration of therapeutic doses of omeprazole in parallel with inhibition of acid secretion. Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found to date.
B.)PHARMACOLOGY:
Absorption: – The delayed-release capsule are enteric-coated (as omeprazole is acid-labile) so the absorption of omprazole begins once the granules leave the stomach. Absorption is rapid. Peak plasma levels occur within 0.5 – 3.5 hours. The absolute bioavailability (compared with intravenous administration) of the delayed-release capsule is 30-40% at doses of 20 – 40 mg, due to presystemic metabolism. This value increases slightly when given repeatedly. Based on a relative bioavailability study, the AUC and Cmax of PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension were 87% and 88% of those for PRILOSEC Delayed-Release Capsules, respectively. Interestingly, when the 40 mg delayed release capsule is given with or without applesauce, it is bioequivalent. However, when the 20 mg delayed release capsule is given with the same conditions, it is not bioequivalent. When the same capsule is given to the elderly, bioavailability increases. Omeprazole was 76% bioavailable.
Protein Binding: – 95% bound to human plasma protein.
Metabolism: – Hepatic. Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system. The two primary CYP isozymes involved are CYP2C19 and CYP3A4. Metabolism is stereo selective in which the S-isomer is converted to 5’O-desmethylomeprazole via CYP2C19. CYP3A4 converts the S-isomer to 3-hydroxyomeprazole. The R-isomer is converted to 5-hydroxyomeprazole by CYP2C19. CYP3A4 converts the R-isomer to any four different metabolites: 5-hydroxyomeprazole (5-OH OME), omeprazole sulfone (OME sulfone), 5′-O-desmethylomeprazole (5′-desmethyl OME), and 3-hydroxyomeprazole (3-OH OME).
Route of Elimination: – Urinary excretion is a primary route of excretion of omeprazole metabolites. Little, if any unchanged drug was excreted in the urine. The majority of the dose (about 77%) was eliminated in urine as at least six metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was recovered in the feces.
Half-Life: – 0.5-1 hour (healthy subjects, delayed-release capsule); 3 hours (hepatic impairment)
INDICATIONS:
Omeprazole is indicated for the treatment of duodenal ulcers, benign gastric ulcers, gastroesophageal reflux disease (GERD), heartburn and other symptoms associated with GERD.
Erosive esophagitis and long-term treatment of pathological hypersecretory conditions like Zollinger-Ellison syndrome, multiple endocrine adenomas, and systemic mastocytosis.
