title: Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome.
abstract: OBJECTIVE
  In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES.
  
  
  METHODS
  The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery).
  
  
  RESULTS
  The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2.
  
  
  CONCLUSIONS
  There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required.
authors.affiliation: Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Metz
authors.forename: C
authors.initials: C
authors.lastname: Forsmark
authors.forename: E A
authors.initials: EA
authors.lastname: Lew
authors.forename: J A
authors.initials: JA
authors.lastname: Starr
authors.forename: E F
authors.initials: EF
authors.lastname: Soffer
authors.forename: W
authors.initials: W
authors.lastname: Bochenek
authors.forename: J R
authors.initials: JR
authors.lastname: Pisegna
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D019233:Retreatment; D013454:Sulfoxides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D000077402:Pantoprazole; D009853:Omeprazole