The influence of variable gastric emptying and intestinal transit rates on the plasma level curve of cimetidine; an explanation for the double peak phenomenon
dc.contributor.author | Oberle, Rebecca L. | en_US |
dc.contributor.author | Amidon, Gordon L. | en_US |
dc.date.accessioned | 2006-09-11T15:35:52Z | |
dc.date.available | 2006-09-11T15:35:52Z | |
dc.date.issued | 1987-10 | en_US |
dc.identifier.citation | Oberle, Rebecca L.; Amidon, Gordon L.; (1987). "The influence of variable gastric emptying and intestinal transit rates on the plasma level curve of cimetidine; an explanation for the double peak phenomenon." Journal of Pharmacokinetics and Biopharmaceutics 15(5): 529-544. <http://hdl.handle.net/2027.42/45037> | en_US |
dc.identifier.issn | 1573-8744 | en_US |
dc.identifier.issn | 0090-466X | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/45037 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=3694496&dopt=citation | en_US |
dc.description.abstract | A physiological flow model is presented to account for plasma level double peaks based on cyclical gastric emptying and intestinal motility in the fasted state. Central to the model is the assumption that gastric emptying and intestinal transit rates will vary directly with the strength of the contractile activity characteristic of the fasted state motility cycle. Simulated curves clearly indicate that variable gastric emptying rates can result in variable absorption rates from the gastrointestinal tract and double peaks in the plasma level curves of cimetidine. Vital to the occurrence of double peaks are (i) dosing time relative to phasic activity, (ii) variability in flow out of the stomach, and (iii) a small emptying rate constant Q s /V s , for a period of time within the first hour after administration. Variability in intestinal flow rates alone does not cause a double peak in the plasma level curve. Results of the simulations, as well as experimental results, can be categorized according to the shapes of the plasma level curves into four types: type A, C pmax (1) <C pmax (2); type B, single peak; type C, C pmax (1)>C pmax (2); type D, C pmax (1)=C pmax (2). Assuming that the experimental results were obtained from fasted subjects, with the time of dose administration being a random variable, the frequency of the experimental curves having shape A, B, C, or D correlates extremely well with theoretical predictions. It is concluded that variable gastric emptying rates due to the motility cycle can account for plasma level double peaks. Furthermore, variable gastric emptying rates combined with the short plasma elimination half-life and poor gastric absorption of cimetidine can be the cause of the frequently observed plasma level double peaks. | en_US |
dc.format.extent | 875860 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 | Veterinary Medicine | en_US |
dc.subject.other | Biomedical Engineering | en_US |
dc.subject.other | Gastric Emptying | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Biomedicine | en_US |
dc.subject.other | Pharmacy | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Cimetidine | en_US |
dc.subject.other | Oral Absorption | en_US |
dc.subject.other | Double Peaks | en_US |
dc.subject.other | Fasted Motility | en_US |
dc.title | The influence of variable gastric emptying and intestinal transit rates on the plasma level curve of cimetidine; an explanation for the double peak phenomenon | 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 | College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, 48109-1065, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 3694496 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/45037/1/10928_2005_Article_BF01061761.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/BF01061761 | en_US |
dc.identifier.source | Journal of Pharmacokinetics and Biopharmaceutics | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.