Effect of histamine-H2 receptor antagonists on serum gastrin levels in swine.
We evaluated the serum gastrin response to feeding and increasing age in swine. In addition, metiamide (SKF 92058) and the more potent H2 receptor antagonist, SKF 93479, were administered in the feed after which, serum was evaluated for changes in gastrin. We also measured metiamide clearance from the blood after an intravenous bolus infusion of the drug. Gastrin levels measured 15 minutes after feeding decreased as a consequence of increasing animal age (P less than 0.0001). Postprandial serum gastrin levels increased to maximal levels by approximately 60 minutes postfeeding and declined slowly during the subsequent 60 minutes. There were no differences in the postprandial gastrin responses during the morning or evening feeding, although evening levels tended to be higher (P greater than 0.10). Metiamide fed at 50 or 500 mg/kg of feed caused a significant increase (P less than 0.02) in gastrin 15 minutes postfeeding (31.0 and 39.7%, respectively). Metiamide in serum decreased to undetectable levels by 120 minutes after an intravenous infusion of 10 mg/kg in two pigs. Metiamide fed at 162 mg/kg and SKF 93479 fed at 54 mg/kg of ration resulted in similar elevations in gastrin, indicating that SKF 93479 was as potent as metiamide in eliciting a gastrin response by using only one-third of the concentration in the feed. These results provide evidence for similarities between swine and humans in serum gastrin responses.
Zavy
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Applebrook Research Center, Smith Kline, Beecham Animal Health Products, West Chester, PA 19380.
Hedde
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D000367:Age Factors; D000818:Animals; D005755:Gastrins / Q000097:blood*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008785:Metiamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D013045:Species Specificity; D013552:Swine
D005755:Gastrins; D006635:Histamine H2 Antagonists; D011744:Pyrimidinones; D008785:Metiamide; C033275:SK&F 93479