Intestinal absorption of peptides and peptide analogues: implications of fasting pancreatic serine protease levels and pH on the extent of oral absorption in dogs and humans.
In order to describe and predict the impact of intestinal metabolism on peptide absorption, intestinal chymotrypsin activity, flow rate, and pH were characterized in fasted, duodenally fistulated dogs as a function of gastrointestinal (GI) motility phase. GI motility was classified as either active or quiescent. Cumulative volume, F(t), and volumetric flow rate, Q(t), curves were constructed and the data were sorted according to motility phase. The mean +/- SE active phase pH was 6.4 +/- 0.3, whereas the quiescent phase pH was 7.3 +/- 0.3. The difference between the mean active and the mean quiescent phase pH values was significant. The active and quiescent phase flow rates (ml/min) were also significantly different, at values of 1.2 +/- 0.2 and 0.28 +/- 0.07, respectively. The active phase flow rates were consistent among the dogs studied; however, the quiescent phase flow rates were highly variable among the dogs. The variability of the quiescent phase flow rates was expected since phase II of the GI motility cycle is characterized by intermediate, irregular spike activity. The mean active and quiescent phase chymotrypsin activities were 1.87 x 10(-5) +/- 0.53 x 10(-5) and 1.56 x 10(-5) +/- 0.65 x 10(-5) M, respectively. The active phase values were not statistically different among dogs, however, the quiescent phase values were found to be highly variable among dogs. The difference between the active and the quiescent phase chymotrypsin mean levels, however, was not statistically significant. The chymotrypsin levels determined in dogs were found to be approximately 10 times greater than those reported in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Sinko
P J
PJ
Therapeutic Systems Research Laboratories, Inc., Ann Arbor, Michigan 48108.
D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D002918:Chymotrypsin / Q000032:analysis*; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption / Q000502:physiology*; D010179:Pancreas / Q000201:enzymology; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*
D010455:Peptides; D002918:Chymotrypsin