Comparison between the synthetic cholecystokinin analogues caerulein and Thr28NlE31CCK25-33(CCK9) with regards to plasma bioactivity, degradation rate and stimulation of pancreatic exocrine function.
A new synthetic analogue of cholecystokinin, Thr28Nle31CCK25-33(CCK9) is compared with caerulein with regards to plasma bioactivity, degradation rate, side effects, and stimulation of pancreatic secretion. 24 healthy male volunteers were intubated with a double lumen Lagerlöf-tube. 30 min after correct positioning of the tube subjects received a continuous intravenous infusion of synthetic secretin (1 U/kg) together with either ceruletide (61.5 pM/kg) or CCK9 (30 pM/kg) both for 45 min. 30 pM/kg of CCK9 have been shown by others to cause maximal enzyme secretion (1). 61.5 pM/kg (= 100 ng) of caerulein are probably supramaximal but used by many centers for direct pancreatic function tests. Plasma CCK was measured by bioassay which compares amylase release of isolated rat pancreatic acini stimulated by plasma extracts with known standards of CCK8. Lipase, amylase, trypsin, chymotrypsin, and bicarbonate were measured in 15 min fractions after the onset of CCK infusion. Both drugs caused a similar stimulation of pancreatic enzyme secretion during infusion of the respective analogue which declined after termination. After the onset of CCK9 infusion plasma bioactivity reached a plateau around 20 pM at 15 min. Values declined after 30 min. After termination of infusion bioactivity rapidly declined within 3 min but still remained slightly elevated after further 15 min as compared to basal values (3.9 vs 0.6 pM). Plasma kinetics of caerulein were quite similar. However, despite a dose which was only twice as high as compared to CCK9, plasma bioactivity was six times higher with plateau values of about 120 pM.(ABSTRACT TRUNCATED AT 250 WORDS)
Mössner
J
J
Medizinische Poliklinik, University of Würzburg.
Sprenger
C
C
Secknus
R
R
Kestel
W
W
Fischbach
W
W
D000328:Adult; D000681:Amylases / Q000097:blood; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001682:Biological Availability; D002108:Ceruletide / Q000493:pharmacokinetics* / Q000494:pharmacology; D002766:Cholecystokinin / Q000493:pharmacokinetics* / Q000494:pharmacology; D002918:Chymotrypsin / Q000097:blood; D046508:Culture Techniques; D006801:Humans; D007262:Infusions, Intravenous; D007419:Intestinal Secretions / Q000187:drug effects; D008049:Lipase / Q000097:blood; D008297:Male; D010179:Pancreas / Q000187:drug effects*; D010186:Pancreatic Function Tests; D010446:Peptide Fragments / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014357:Trypsin / Q000097:blood
D001639:Bicarbonates; D010446:Peptide Fragments; C053399:cholecystokinin 9; D002108:Ceruletide; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases; D002918:Chymotrypsin; D014357:Trypsin