Inhibitory effect of intraduodenal infusion of loxiglumide on pancreatic exocrine secretion.
Inhibitory effect of loxiglumide (D,L-4-(3, 4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylamino)-5- oxo-pentanoic acid, CAS 107097-80-3) on exocrine pancreatic secretion was compared between intraduodenal and intravenous administration. Doubling doses of intravenous cholecystokinin octapeptide (CCK-8) resulted in a dose-dependent increase of pancreatic secretion from 50 to 400 ng/kg/h. Both intraduodenal and intravenous loxiglumide of 5 and 10 mg/kg/h produced a dose-dependent inhibition of the pancreatic protein secretion to all doses of CCK-8. Cumulative increment of pancreatic protein output was inhibited by 79% and 77% at 10 mg/kg/h of intraduodenal and intravenous loxiglumide, respectively. Extents of the inhibition were similar to each other between the two routes of loxiglumide infusion. However, plasma levels of loxiglumide after intraduodenal administration were about half of those observed after intravenous administration of the corresponding dose, although plasma CCK levels were not different. Intraduodenal loxiglumide is as effective as intravenous loxiglumide in inhibitory potency on pancreatic secretion. Therefore, possible therapeutic indications of oral loxiglumide could be expected.
Tanikawa
M
M
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hayakawa
T
T
Kondo
T
T
Shibata
T
T
Kitagawa
M
M
Kodaira
T
T
Hamaoka
T
T
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D004285:Dogs; D004386:Duodenum; D005260:Female; D007262:Infusions, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism
D011506:Proteins; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide