Risek/Risek Insta Mechanism of Action

Pharmacotherapeutic Group: Omeprazole, a substituted benzimidazole, is a proton-pump inhibitor that inhibits gastric acid secretion.
Pharmacology: Mechanism of Action: Omeprazole reduces gastric acid secretion through a unique mechanism of action. Omeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles that do not exhibit anticholinergic or histamine antagonistic properties. It inhibits secretion of gastric acid by irreversibly blocking the enzyme system of hydrogen/potassium adenosine triphosphate (H⁺/K⁺ ATPase), the proton pump of the gastric parietal cell. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Pharmacokinetics: Absorption and Distribution: Risek: Risek capsule is acid-labile and administered orally as enteric-coated pellets in capsules. Omeprazole is rapidly but variably absorbed following oral administration, with peak plasma levels of omeprazole occurring within 0.5-3.5 hrs. Absorption of omeprazole is not affected by food and also appears to be dose dependent. Increasing the dosage >40 mg has been reported to increase the plasma concentrations in a nonlinear fashion because of saturable first-pass metabolism. Absorption is higher after long-term administration.
The systemic bioavailability of omeprazole is approximately 35%. After repeated once-daily administration, the bioavailability increases to about 60%. The plasma protein-binding of omeprazole is about 95%.
Risek Insta: Omeprazole is acid-labile and is administered orally on an empty stomach 1 hr prior to a meal. The absorption of omeprazole is rapid, with mean peak plasma levels being 1954 ng/mL (33%) occurring at about 30 min (range 10-90 min) after a single-dose or repeated-dose administration. Absolute bioavailability of omeprazole powder for oral suspension is about 30-40% at doses 20-40 mg due in large part to presystemic metabolism. When powder for oral suspension is administered 1 hr after a meal, the omeprazole area under the concentration-time curve (AUC) is reduced by approximately 24% relative to administered 1 hr prior to meal.
Omeprazole is bound to plasma proteins. Protein-binding is approximately 95%.
Metabolism and Excretion: Following absorption, omeprazole is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19 to form hydroxy-omeprazole and to a small extent by CYP3A to form omeprazole sulfone. These metabolites are inactive and excreted mostly in the urine and to a lesser extent in the bile. The majority of the dose (about 77%) is eliminated in the urine and the remainder recoverable in the feces.
Risek: The elimination half-life (t_½) from plasma following oral administration is reported to be about 0.5-3 hrs. The elimination t_½ from plasma following IV administration is approximately 40 min to 3 hrs. The total plasma clearance is 0.3-0.6 L/min. There is no change in t_½ during treatment.
Risek Insta: The mean plasma omeprazole half-life (t_½) is approximately 1 hr (ranging from 0.4-3.2 hrs) and the total body clearance is 500-600 mL/min.
Special Population: Pediatric: Risek: Available data from children (≥1 year) suggest that the pharmacokinetics within the recommended doses are similar to those in adults. At steady-state, lower plasma levels of omeprazole were seen in some children.
There is limited experience with omeprazole administered IV in children.
Risek Insta: The pharmacokinetics of omeprazole has not been studied in patients <18 years.
Geriatric: Risek: The bioavailability of omeprazole may be increased in elderly patients.
In elderly patients, the volume of distribution (V_d) is slightly decreased as compared to healthy patients. Dose adjustment is not needed in the elderly.
Risek Insta: The elimination rate of omeprazole was somewhat decreased in the elderly and bioavailability was increased. Omeprazole was 76% bioavailable when a single oral dose of omeprazole 40 mg (buffered solution) was administered to healthy elderly subjects, versus 58% in young subjects given the same dose. The plasma clearance of omeprazole was 250 mL/min (about ½ that of young subjects) and its plasma half-life (t½) averaged 1 hr, similar to that of young healthy subjects.
Renal Insufficiency: Risek: The systemic bioavailability of omeprazole is not significantly altered in patients with reduced renal function. The V_d in patients with reduced renal function is similar to that seen in healthy patients. Therefore, dose adjustment is not required.
Risek Insta: In patients with chronic renal impairment, whose creatinine clearance (CrCl) ranged between 10 and 62 mL/min/1.73 m², the disposition of omeprazole from a buffered solution was very similar to that in healthy subjects, although there was a slight increase in bioavailability. Because urinary excretion is a primary route of excretion of omeprazole metabolites, their elimination slowed in proportion to the decreased CrCl.
Hepatic Insufficiency: Risek: The area under the plasma concentration-time curve (AUC) is increased in patients with impaired liver function, but no tendency to accumulation of omeprazole has been found.
The V_d is slightly decreased, while the plasma t_½ of omeprazole is increased.
Risek Insta: In patients with chronic hepatic disease, the bioavailability of omeprazole from a buffered solution increased to approximately 100% and the mean plasma t_½ of the drug increased to nearly 3 hrs compared to the mean t½ of 1 hr in normal subjects. Plasma clearance averaged 70 mL/min, compared to a value of 500-600 mL/min in normal subject.