Oral Bioavailability of Pantoprazole Suspended in Sodium Bicarbonate Solution

Geraldine M. Ferron, Sherry Ku, Madelyn Abell, Mary Unruh, John Getsy, Philip R. Mayer, Jeffrey Paul


Am J Health Syst Pharm. 2003;60(13) 

In This Article

Abstract and Introduction

The bioavailability of pantoprazole when administered as a suspension in sodium bicarbonate solution and as the oral tablet was studied.

In an open-label, randomized, two-period crossover study, healthy fasting subjects received either one enteric-coated 40-mg pantoprazole tablet by mouth with 240 mL of water or 20 mL of a suspension prepared from one crushed pantoprazole tablet and 840 mg of sodium bicarbonate solution and administered via a nasogastric tube. Treatments were separated by a 48-hour washout period. Blood samples were collected at intervals up to 24 hours after drug administration for measurement of pantoprazole concentration by high-performance liquid chromatography (HPLC) and estimation of pharmacokinetic values. A separate study was conducted to determine pantoprazole's stability in the suspension for up to three months at 25, 5, and –20 °C; concentrations were measured by HPLC.

Twelve subjects completed the study. The suspension yielded pantoprazole Cmax values similar to those of the tablet formulation, but the drug was 25% less bioavailable. There was no lag time for the suspension. The suspension was stable for up to two weeks at 5 °C and up to three months at °20 °C.

A suspension of pantoprazole in sodium bicarbonate solution yielded a Cmax similar to that of the tablet formulation, and the drug was quickly absorbed. However, bioavailability was slightly lower with the suspension than with the tablet.

Pantoprazole is a substituted benzimidazole derivative that targets gastric acid proton pumps, the final common pathway for gastric acid secretion.[1] The drug binds irreversibly to the proton pumps, causing prolonged inhibition of gastric acid secretion.[2,3] The oral delayed-release dosage form (entericcoated tablet) of this proton-pump inhibitor (PPI) has received FDA-approved labeling for use in short-term and maintenance therapy of erosive esophagitis associated with gastroesophageal reflux disease, as well as for the treatment of pathological hypersecretion associated with Zollinger-Ellison syndrome.[4,5] An intravenous formulation, which is provided as a lyophilized powder, is also indicated for use in the short-term treatment of patients who are unable to continue oral therapy.[5] For some patients, such as elderly people and children who cannot swallow intact tablets, an oral suspension may be a useful alternative, assuming that the gastrointestinal tract is functioning well enough to absorb the medication.

Delayed-release pantoprazole (Protonix, Wyeth-Ayerst Laboratories) is prepared as an enteric-coated tablet so that drug absorption begins only after the tablet leaves the stomach.[6] Pantoprazole is rapidly eliminated; the half-life (t1/2) is approximately one hour.[6] The pharmacokinetics are linear over a dose range of 5-80 mg and are not altered by multiple administrations.[7] The absolute bioavailability of the enteric-coated tablet is 77% after a single dose and similar after multiple administrations. Concomitant intake of food and antacids does not influence the area under the concentration-versus-time curve (AUC), maximum concentration (Cmax), or bioavailability.[6]

Pantoprazole, like other PPIs, has optimum stability at a pH of 9. At a pH of 1-2, pantoprazole degrades within minutes.[8] This is why all PPIs are formulated as gastric acid-resistant formulations for oral administration. Administration of an antacid before administration of PPIs as a solution prevented their gastric acid degradation and maintained their oral bioavailability.[6,9] Neutralization of gastric acid by a total of 87 meq of sodium bicarbonate solution administered before, during, and after patoprazole administration resulted in 93% absolute bioavailability.[9] We thus hypothesized that the pharmacokinetics of pantoprazole given as a suspension in sodium bicarbonate solution would be similar to those of the tablet. Studies of omeprazole and lansoprazole found that the drugs, when given as aqueous sodium bicarbonate suspensions through gastrostomy tubes, were 58-81% bioavailable (omeprazole) and 68-85% bioavailable (lansoprazole) compared with the tablet formulation and effective in raising intragastric pH.[10,11]

The purpose of this study was to compare the bioavailability of pantoprazole when administered as a suspension in sodium bicarbonate solution and as the oral tablet.