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(±)-Pantoprazole sodium, ((±)-PANNa), is a proton pump inhibitor that is administered as a racemate. The protective effects of (-)-PANNa, (+)-PANNa and (±)-PANNa on various experimental ulcers in animals were compared. (-)-PANNa inhibited gastric lesions induced by water-immersion stress, aspirin, ethanol, and reserpine in a dose-dependent manner. The dose that inhibited 50% of lesions (ID50) were 2.72 ± 1.03, 1.60 ± 0.64, 4.12 ± 2.18, and 2.77 ± 0.86 mg/kg, respectively. The ID50 values of (+)-PANNa and (±)-PANNa were 1.7, 2.6, 1.8, 2.7 and 1.5, 1.7, 1.6, 1.9 times higher, respectively, than that of (-)-PANNa. Primary culture of rat gastric epithelial cells was investigated as an in vitro model for comparing the cell protective effects among the three agents. Exposed to the three drugs at the concentrations of 2.5 × 10-1-2.5 × 10-5 mg/ml, cultured cells were treated with either pH 3.5 me- dium or 3.5 mM indomethacin. Cytoprotection was evaluated by MTT. (-)-PANNa, (+)-PANNa and (±)-PANNa provided significant cytoprotective effects when the cells were pretreated with the drugs prior to exposure to 3.5 mM indomethacin, whereas, when they were treated concurrently, no significant cytoprotective effects were found. In pH 3.5 medium-induced damage, the three drugs had marked protective effects on gastric cells, however, when the concentration of drugs was high (0.25 mg/ml), only (+)-PANNa had significant cytoprotection. We concluded that the cytoprotective mechanisms of (-)-PANNa and (+)-PANNa are different. The results of in vitro experiments were not in complete accordance with the in vivo results, suggesting that the effects of the three drugs on ulcer inhibition are mainly due to the effects of acid inhibition rather than cytoprotection.

Comparison of the Effects of Pantoprazole Enantiomers on Gastric Mucosal Lesions and Gastric Epithelial Cells in Rats