Gastric pH Influences the Appearance of Double Peaks in the Plasma Concentration-Time Profiles of Cimetidine After Oral Administration in Dogs
dc.contributor.author | Mummaneni, Vanaja | en_US |
dc.contributor.author | Dressman, Jennifer B. | en_US |
dc.contributor.author | Amidon, Gordon L. | en_US |
dc.date.accessioned | 2006-09-08T19:15:53Z | |
dc.date.available | 2006-09-08T19:15:53Z | |
dc.date.issued | 1995-05 | en_US |
dc.identifier.citation | Mummaneni, Vanaja; Amidon, Gordon L.; Dressman, Jennifer B.; (1995). "Gastric pH Influences the Appearance of Double Peaks in the Plasma Concentration-Time Profiles of Cimetidine After Oral Administration in Dogs." Pharmaceutical Research 12(5): 780-786. <http://hdl.handle.net/2027.42/41444> | en_US |
dc.identifier.issn | 1573-904X | en_US |
dc.identifier.issn | 0724-8741 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/41444 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=7479568&dopt=citation | en_US |
dc.description.abstract | The plasma concentration-time profiles of cimetidine often exhibit two peaks following oral administration of a single dose in the fasted state, while the concurrent administration of some antacids results in a lower extent as well as rate of absorption. In the present work, absorption of cimetidine after a single dose in the fasted state was studied as a function of gastric pH in male beagle dogs to determine whether gastric pH plays a role in the double peak phenomenon and/or can account for the decrease in bioavailability when antacids are coadministered. The extent of absorption of cimetidine was not influenced significantly by gastric pH, indicating that elevation of gastric pH is not the cause of decreases in the bioavailability of cimietidine when it is administered with antacids. Distinct double peaks or plateaux were noted in 8 of 10 plasma profiles when the gastric pH was 3 or below. Irregular absorption behavior was observed in 2 of 6 profiles in the pH range of 3 to 5, while single peaks were observed in all 10 profiles when the gastric pH was maintained at pH ≥ 5. It was concluded that gastric pH is a major factor in the generation of cimetidine double peaks. Changes in gastric pH also resulted in changes in the apparent kinetics of absorption. Below pH 5, absorption mostly followed zero-order kinetics (9 of 16 profiles) or a more complex kinetic process involving at least two components to the absorption phase (5 of 16 profiles). At gastric pH ≥ 5, however, absorption followed first order kinetics in 7 of 10 profiles. These differences in kinetics of absorption are postulated to arise from variations in gastric emptying as a function of pH and/or carryover effects of gastric pH into the upper intestine. | en_US |
dc.format.extent | 1245611 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 | Cimetidine | en_US |
dc.subject.other | Bioavailability | en_US |
dc.subject.other | Pharmacy | en_US |
dc.subject.other | Gastric PH | en_US |
dc.subject.other | Double Peaks | en_US |
dc.subject.other | Biomedical Engineering | en_US |
dc.subject.other | Medical Law | en_US |
dc.subject.other | Absorption Rate Constant | en_US |
dc.subject.other | Biochemistry, General | en_US |
dc.subject.other | Pharmacology/Toxicology | en_US |
dc.subject.other | Intestinal PH | en_US |
dc.subject.other | Biomedicine | en_US |
dc.subject.other | Gastric Emptying | en_US |
dc.title | Gastric pH Influences the Appearance of Double Peaks in the Plasma Concentration-Time Profiles of Cimetidine After Oral Administration in Dogs | 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, Ann Arbor, Michigan, 48109-1065; Institut für Pharmazeutische Technologic, J. W. Goethe-Universität, Marie Curie Str. 9, D-60439, Frankfurt am Main, Germany | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, 48109-1065; Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543-4000 | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan, 48109-1065 | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 7479568 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/41444/1/11095_2004_Article_306899.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1023/A:1016284214708 | en_US |
dc.identifier.source | Pharmaceutical Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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