Document Detail


Evaluation of the effect of 3 different diets on the bioavailability of 2 sustained release theophylline matrix tablets.
MedLine Citation:
PMID:  9455715     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Food-induced changes on bioavailability of 2 sustained release theophylline matrix tablets, which uses an hydrophilic matrix of Carbopol 974P and lipid matrix of hydrogenated castor oil (Cutina HR) as sustaining agents, have been studied in 2 different groups of 12 healthy male volunteers. The study design was a 4 x 4 Latin square involving 12 subjects who received a single dose of the tablet while fasting or with a standarized normal, high fat or high fat/high protein meal. The results for both formulations showed no differences in t1/2 and MRT when the tablets were administered with any type of diet. No differences in tmax and AUC were found when the Carbopol matrix tablet was administered with any class of diet. Higher Cmax were obtained when the tablet was administered with any class of meal. The analysis of the ratio Cmax/AUC evidenced that changes in Cmax for normal and high fat diet were attributable to higher rate of absorption, probably due to a delay in gastric emptying, thus avoiding the rapid formation of the gel structure which controls the liberation of theophylline. Three subjects showed a probable bioadhesive behavior of the formulation in the fasted condition. The lipid matrix tablet showed a statistical significant delay in tmax comparing the fasted condition with the different diets. AUC, Cmax, and the ratio Cmax/AUC did not change when the tablet was administered with the normal diet. High fat and high fat/high protein diets produced higher AUC (31% and 40%, respectively) and Cmax (40% and 56%, respectively) than under fasting condition. The analysis of the ratio Cmax/AUC indicated that changes in Cmax were more probably due to changes in the amount absorbed. In conclusion, a sustained-release theophylline tablet formulated as a lipid matrix is affected by any meal with a high fat content, probably because of the increase of pancreatic and biliary secretions promoted by the meal that would affect the matrix itself. Normal diet showed this behavior but only as a nonsignificant trend. It seems appropiate to recommend to dose both formulations at least 2 hours before meal, or under consistent conditions of fasting or nonfasting state to assure reproducible absorption or clinical response.
Authors:
M N Gai; A Isla; M T Andonaegui; A M Thielemann; C Seitz
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  35     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-03-24     Completed Date:  1998-03-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  565-71     Citation Subset:  IM    
Affiliation:
Department of Science and Pharmaceutical Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
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MeSH Terms
Descriptor/Qualifier:
Area Under Curve
Biological Availability
Bronchodilator Agents / administration & dosage,  blood,  pharmacokinetics*
Cross-Over Studies
Delayed-Action Preparations
Diet
Dietary Fats / administration & dosage
Dietary Proteins / administration & dosage
Fasting
Food-Drug Interactions*
Gastric Emptying / physiology
Humans
Intestinal Absorption
Lipid Metabolism
Lipids / chemistry
Male
Tablets
Theophylline / administration & dosage,  blood,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Bronchodilator Agents; 0/Delayed-Action Preparations; 0/Dietary Fats; 0/Dietary Proteins; 0/Lipids; 0/Tablets; 58-55-9/Theophylline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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