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
dc.contributor.author | Sinko, Patrick J. | en_US |
dc.date.accessioned | 2006-09-08T19:24:05Z | |
dc.date.available | 2006-09-08T19:24:05Z | |
dc.date.issued | 1992-03 | en_US |
dc.identifier.citation | Sinko, Patrick J.; (1992). "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." Pharmaceutical Research 9(3): 320-325. <http://hdl.handle.net/2027.42/41569> | en_US |
dc.identifier.issn | 0724-8741 | en_US |
dc.identifier.issn | 1573-904X | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/41569 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1614964&dopt=citation | en_US |
dc.description.abstract | 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 × 10 -5 ± 0.53 × 10 -5 and 1.56 × 10 -5 ± 0.65 × 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. The significance of fasted-state chymotrypsin levels is discussed with respect to the impact of GI metabolism on peptide and peptide-like drug absorption in dogs. Further, given the intestinal metabolic differences between dogs and humans, the suitability of using the dog model for predicting the oral absorption of peptides in humans is discussed. | en_US |
dc.format.extent | 1082862 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers-Plenum Publishers; Plenum Publishing Corporation ; Springer Science+Business Media | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Peptide-like Drugs | en_US |
dc.subject.other | Human | en_US |
dc.subject.other | Chymotrypsin | en_US |
dc.subject.other | Biomedicine | en_US |
dc.subject.other | Dog | en_US |
dc.subject.other | Intestinal Metabolism | en_US |
dc.subject.other | Pharmacy | en_US |
dc.subject.other | Oral Absorption | en_US |
dc.subject.other | Pancreatic Serine Protease | en_US |
dc.subject.other | Peptide | en_US |
dc.subject.other | Biomedical Engineering | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Medical Law | en_US |
dc.title | 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 | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Therapeutic Systems Research Laboratories, Inc., 540 Avis Drive, Suite A, Ann Arbor, Michigan, 48108; College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, 48109; College of Pharmacy, Rutgers University, P.O. Box 789, Piscataway, New Jersey, 08855-0789 | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 1614964 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/41569/1/11095_2004_Article_305100.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1023/A:1015830600227 | en_US |
dc.identifier.source | Pharmaceutical Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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