Sign Out
Pharmacology: Pharmacodynamics: Nexpro-20/Nexpro-40: Esomeprazole, the S-isomer of omeprazole, reduces gastric acid secretion through specific inhibition of the acid pump in the parietal cell, where it is concentrated and converted to the active form in the acidic environment of the secretory canaliculi and inhibits the enzyme H+K+ ATPase the proton pump. This effect on the final step of the gastric secretion is dose-dependent and provides for effective inhibition of both basal and stimulated acid secretion.
Effects on Gastric acid secretion: After oral dosing with esomeprazole 20mg and 40mg the onset of effects occurs within 1 hour. After repeated administration with 20mg esomeprazole once daily for 5 days, mean acid output after pentagastrin stimulation is decreased by 90% when measured 6-7 hours after dosing on day 5. After 5 days of oral dosing with 20mg and 40mg of esomeprazole, intragastric pH above 4 was maintained for a mean time of 13 hours and 17 hours, respectively over 24 hours in symptomatic gastro-esophageal reflux disease (GERD) patients. The proportion of patients maintaining an intragastric pH above 4 for at least 8, 12 and 16 hours were 76%, 54% and 24% respectively for esomeprazole 20mg. Corresponding proportions for esomeprazole 40mg were 97%, 92% and 56% respectively.
Using AUC as a surrogate parameter for plasma concentration, a relationship between inhibition of acid secretion and exposure has been shown.
Food intake had no significant influence on the effect of esomeprazole on intragastric acidity.
Other effects related to acid inhibition: During treatment with antisecretory drugs serum gastrin increases in response to the decreased acid secretion. During long-term treatment with antisecretory drugs gastric glandular cysts occur. These changes are a physiological consequence of pronounced inhibition of acid secretion, are benign and appear to be reversible.
Nexpro IV: Mechanism of Action: Esomeprazole is a weak base and is concentrated and converted to the active form in the highly acidic environment of the secretory canaliculi of the parietal cell, where it inhibits the enzyme H+K+-ATPase C the acid pump and inhibits both basal and stimulated acid secretion.
Pharmacokinetics: Nexpro-20/Nexpro-40: Esomeprazole is rapidly absorbed after oral doses, with peak plasma levels occurring after about 1 to 2 hours. Bioavailability of esomeprazole increases with both dose and repeated administration to about 68 and 89% for doses of 20 and 40 mg respectively. Food delays and decreases the absorption of esomeprazole, but this does not significantly change its effect on intragastric acidity. Esomeprazole is about 97% bound to plasma proteins. It is extensively metabolized in the liver by the cytochrome P450 isoenzyme CYP2C19 to hydroxy and desmethyl metabolites, which have no effect on gastric acid secretion. The remainder is metabolized by the cytochrome P450 isoenzyme CYP3A4 to esomeprazole sulfone. With repeated dosage, there is a decrease in first-pass metabolism and systemic clearance, probably caused by an inhibition of the CYP2C19 isoenzyme.
However, there is no accumulation during once daily use. The plasma elimination half-life is about 1.3 hours. Almost 80% of an oral dose is eliminated as metabolites in the urine, the remainder in the feces.
Geriatric Patients: The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years of age).
Patients with renal impairment: No studies have been reported in patients with decreased renal function. Since the kidney is responsible for the excretion of the metabolites of esomeprazole, but not for the elimination of the parent compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired renal function.
Patients with hepatic impairment: The metabolism of esomeprazole in patients with mild to moderate liver dysfunction may be impaired. The metabolic rate is decreased in patients with severe liver dysfunction resulting in a doubling of the area under the plasma concentration-time curve of esomeprazole. Therefore, a maximum of 20 mg should not be exceeded in patients with severe dysfunction.
Pharmacogenetics: Approximately 1-2% of the population lack a functional CYP2C19 enzyme and are called poor metabolizers. In these individuals, the metabolism of esomeprazole is probably mainly catalyzed by CYP3A4. It is reported that after repeated once-daily administration of 40mg esomeprazole, the mean area under the plasma concentration-time curve was approximately 100% higher in poor metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers). Mean peak plasma concentrations were increased by about 60%.
