| The talinolol double-peak phenomenon is likely caused by presystemic processing after uptake from gut lumen. | |
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MedLine Citation:
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PMID: 15906167 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Evaluation of the double-peak phenomenon during absorption of the beta(1)-selective blocker talinolol relative to paracetamol, which is well absorbed from all parts of the gut, and relative to vitamin A, which is absorbed via the lymphatic pathway. METHODS: Talinolol was given with paracetamol and retinyl palmitate in fast-disintegrating, enteric-coated, and rectal soft capsules to 8 fasting male healthy subjects (21-29 years, 68-86 kg). To evaluate whether the talinolol double-peak is associated with processes of food absorption, a breakfast was served 1 h after administration of a fast disintegrating capsule. RESULTS: Bioavailability of talinolol in enteric-coated and rectal capsules was significantly reduced by about 50% and 80%, respectively, despite unchanged bioavailability of paracetamol. Double-peaks appeared after 2-3 h and 4-6 h with talinolol given as fast-liberating capsules. Food increased the maximum concentrations significantly (223 +/- 76 microg/ml vs. 315 +/- 122 microg/ml, p < 0.05) and shifted the second peak of talinolol to shorter t(max) values (3.8 +/- 1.2 h vs. 2.1 +/- 0.6 h, p < 0.05), which was associated with faster absorption of retinyl palmitate. Pharmacokinetic model fits showed that about half of the oral talinolol dose given with and without meal is drained from the intestine via a presystemic storage compartment. CONCLUSIONS: The double-peak phenomenon of talinolol is likely caused by a presystemic storage compartment, which represents the complex interplay of heterogeneous uptake and kick-back transport processes along the intestinal-hepatic absorption pathway. |
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Authors:
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Werner Weitschies; Annika Bernsdorf; Thomas Giessmann; Michael Zschiesche; Christiane Modess; Vera Hartmann; Claudia Mrazek; Danilo Wegner; Stefan Nagel; Werner Siegmund |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial Date: 2005-05-17 |
Journal Detail:
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Title: Pharmaceutical research Volume: 22 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-05-20 Completed Date: 2005-12-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 728-35 Citation Subset: IM |
Affiliation:
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Department of Biopharmacy and Pharmaceutical Technology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany. werner.weitschies@uni-greifswald.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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administration & dosage,
blood,
pharmacokinetics Administration, Oral Administration, Rectal Adult Area Under Curve Biological Availability Capsules Delayed-Action Preparations / administration & dosage, metabolism, pharmacokinetics Drug Administration Schedule Gelatin Half-Life Humans Intestinal Absorption / drug effects*, physiology* Male Postprandial Period Propanolamines / administration & dosage, blood*, pharmacokinetics* Time Factors Vitamin A / analogs & derivatives, blood |
| Chemical | |
Reg. No./Substance:
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0/Capsules; 0/Delayed-Action Preparations; 0/Propanolamines; 103-90-2/Acetaminophen; 11103-57-4/Vitamin A; 38649-73-9/talinolol; 79-81-2/retinol palmitate; 9000-70-8/Gelatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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