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

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.