Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid-related lesions and acid secretion in rats and guinea-pigs.
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.
Cao
Hong
H
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China.
Wang
Min-Wei
MW
Sun
Li-Xin
LX
Ikejima
Takashi
T
Hu
Zhi-Qing
ZQ
Zhao
Wei-Hua
WH
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D004942:Esophagitis, Peptic / Q000188:drug therapy* / Q000662:veterinary; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D006168:Guinea Pigs; D007536:Isomerism; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000662:veterinary; D013454:Sulfoxides / Q000737:chemistry* / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D000077402:Pantoprazole; D009853:Omeprazole