OMEPRAZOLE NASOGASTRIC ADMINISTRATION PATIENT DATA/BACKGROUND: Can Prilosec (omeprazole) capsules be opened, dissolved in water, and given via nasogastric or a jejunostomy tube?. RESPONSE: Several unique methods have been employed to administer omeprazole capsules to patients who are unable to receive oral medications. One such method is the administration of omeprazole pellets in an alkaline suspension through a jejunostomy tube. However, there are several important pharmaceutical issues to consider before attempting the administration of omeprazole pellets through a nonoral route. Omeprazole is extremely acid labile and degrades rapidly in aqueous solutions with a low pH; at a pH of less than 4 the degradation half-life is 10 minutes, compared to a half-life of 18 hours at pH of 6.5. Early clinical studies used a buffered aqueous suspension to ensure consistent pharmacokinetic properties. This suspension was prepared by using a special micronized form of omeprazole powder suspended in 0.25% methylcellulose and water. Each 50 mL contained 60 mg of omeprazole and 8 mEq of sodium bicarbonate to ensure a pH of 9. This preparation was found to be stable refrigerated for one week. It was necessary to administer the suspension along with additional sodium bicarbonate solution to buffer the gastric pH to neutral for 45 minutes. Therefore, 50 mL (containing 8 mEq) of sodium bicarbonate solution was administered 5, 10, 20, and 30 minutes after each dose, for a total bicarbonate and sodium load of 40 mEq. Administration of a non-buffered suspension resulted in a reduced AUC by 44%, with more than one-half of the dose lost from degradation in the stomach (Pilbrant & Cederberg, 1985). Many of these bioavailability issues have been reolsved with the development of an enteric coated formulation. Omeprazole is available as an enteric-coated tablet or as an enteric-coated granules dispensed in a hard gelatin capsule (Thomson et al, 1997; Pilbrant & Cederberg, 1985). For the capsule formulation, each granule (about 1 mm in diameter) is coated with a sufficient layer of enteric polymer to ensure release at a pH of 6.5 (found in the small intestine). Because the manufacturing process cannot assure that each individual granule is perfectly coated without pin-holes, the granules are enclosed in a hard gelatin capsule, ensuring that only a few pellets out of hundreds are lost (Pilbrant & Cederberg, 1985). Even with the enteric coated formulation, pharmacokinetics are extremely variable between individuals. Peak concentrations and bioavailability can vary 5-fold. Bioavailability consistently increases after repeated dosing due to alkalinization of the gastric contents, but still remains highly variable and unpredictable (Howden et al, 1984). Gastric pH reaches a median of 5.3 after a one-week course of omeprazole, which is still sufficiently acidic to mandate the need for a buffered suspension or intact enteric formulation (Walt et al, 1983). Several unique methods have been employed to administer omeprazole capsules to patients who are unable to receive oral medications. Administering omeprazole pellets down an NG tube may not be effective for the following reasons: Crushed pellets of omeprazole will be inactivated by gastric pH and intact pellets are too large to flush down a NG tube. Additionally, parenteral omeprazole will not be active if administered orally. However, omeprazole pellets administered through a jejunostomy tube has been successful in one institution (Woods & McClintock, 1993). Omeprazole pellets were crushed then added to an alkaline solution such as sodium bicarbonate 8 mmol/50 ml. Upon mixing, the solution was shaken to form a stable suspension. The resultant suspension is then flushed through a jejunostomy tube. Despite the concerns about administering omeprazole through an NG tube, 1 study determined that the bioavailability and gastric acid suppression of oral omeprazole is equal to omeprazole administered through the NG tube. Nasogastric administration of Prilosec(R) was prepared as follows: (1) The granules were removed from the capsules and places in a small dry cup. (2) Six to 10 granules were flushed through the NG tube with 10 to 20 milliliters of water; a total of 140 milliliters was used (Larson et al, 1996). Another study describes the successful administration of omeprazole via a NG tube for the prevention of STRESS-RELATED MUCOSAL DAMAGE in ventilated, critically ill patients. In this study, the contents of one or two 20 milligrams omeprazole capsules were poured into a syringe. Ten to 20 milliliters of an 8.4% sodium bicarbonate solution was withdrawn in the syringe. Thirty minutes were allowed for the enteric-coated omeprazole granules to break down. The resulting milky substance was shaken prior to administration. The NG tube was then flushed with 5 to 10 mL of water then clamped for at least 1 hour. Patients received omeprazole 40 mg once, then 40 mg 6 to 8 hours later, then 20 mg once daily using this technique. The mean gastric pH 4 hours after omeprazole administration was 7.1 whereas the lowest recorded pH after omeprazole administration was 5.6. These values were statistically greater (p less than 0.001) than the mean gastric pH recorded prior the administration of omeprazole (pH=3.5)(Tech Info Prilosec(R), 1997). CONCLUSION: Omeprazole pellets are quickly degraded in the presence of gastric pH; however, the development of enteric coated granule dispensed in a hard gelatin capsule has alleviated these problems. Studies have demonstrated that omeprazole can be administered via NG or jejunostomy tube. REFERENCES: 1. Howden CW, Meredith PA, Forrest JAH et al: Oral pharmacokinetics of omeprazole. Eur J Clin Pharmcol 1984; 26:641-643. 2. Larson C, Cavuto N, Flockhart D et al: Bioavailability and efficacy of omeprazole given orally and by nasogastric tube. Dig Dis Sci 1996; 41:475-479. 3. Pilbrant A & Cederberg C: Development of an oral formulation of omeprazole. Scand J Gastroenterol 1985; 20(Suppl 108):113-120. 4. Technical Information: Prilosec(R), omeprazole. Astra Merck, Wayne, PA, 1997. 5. Thomson ABR, Kirdeikis P, Lastiwka R et al: Pharmacokinetics and pharmacokinetics during treatment with omeprazole 20 mg enteric-coated tablet and 20 mg capsule in asymptomatic duodenal ulcer patients. Can J Gastroenterol 1997; 11(8):657-660. 6. Walt RP, Gomes MFA, Wood ED et al: Effect of daily oral omeprazole on 24 hour intragastric acidity. Br Med J 1983; 287:12-14. 7. Woods DJ & McClintock AD: Omeprazole administration (letter). Ann Pharmacother 1993; 27:651.