Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid-related lesions and acid secretion in rats and guinea-pigs

Abstract

Abstract Pantoprazole is an irreversible proton pump inhibitor that is administered as a racemic mixture clinically. The effects of pantoprazole sodium (PAN·Na) enantiomers on acid-related lesions were compared using models of pylorus ligation induced ulcer, histamine induced ulcer and reflux oesophagitis in rats and guinea-pigs. Compared with (+)-PAN·Na and (±)-PAN·Na, (-)-PAN·Na showed much stronger inhibitory effects on pylorus ligation induced and histamine induced ulcers, but similar effects on reflux oesophagitis. The doses of (-)-PAN·Na, (+)-PAN·Na and (±)-PAN·Na required for 50% inhibition (ID50) of acid-related lesions were 1.28, 5.03 and 3.40 mg kg−1 against pylorus ligation induced ulcer, 1.20, 4.28 and 3.15 mg kg−1 against histamine induced ulcer, and 2.92, 3.56 and 3.70 mg kg−1 against reflux oesophagitis, respectively. The inhibitory effects of PAN·Na enantiomers on basal gastric acid output were compared in rats with acute fistula. In contrast to inhibitory rates of 89.3% and 83.6% on gastric acid output by (-)-PAN·Na and (±)-PAN·Na at 1.5 mg kg−1, (+)-PAN·Na had an inhibitory rate of only 24.7% at the same dose. The above results indicate that (-)-PAN·Na is more potent than (+)-PAN·Na at inhibiting acid-related lesions owing to its stronger inhibition of acid secretion.