Document Detail

Parallel monitoring of plasma and intraluminal drug concentrations in man after oral administration of fosamprenavir in the fasted and fed state.
MedLine Citation:
PMID:  17443397     Owner:  NLM     Status:  MEDLINE    
PURPOSE: The purpose of this study was to explore the feasibility of linking the pharmacokinetic profile of a drug with its gastrointestinal behavior by simultaneously monitoring plasma and intraluminal drug concentrations. Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV-inhibitor amprenavir, was selected as model compound. METHODS: A single tablet of fosamprenavir (Telzir) was administered to 5 volunteers in the fasted and fed state (simulated by intake of a nutritional drink). Gastric and duodenal fluids were aspirated in function of time and characterized with respect to the concentration of (fos)amprenavir, inorganic phosphate and pH. In parallel, blood samples were collected and analyzed for amprenavir. RESULTS: The observed plasma concentration-time profiles suggested a food-induced delay in the absorption of amprenavir: in the fed state, mean tmax increased by more than 150 min compared to the fasted state. A similar delay was seen in the duodenal appearance of fosamprenavir (concentrations in mM-range) and, after dephosphorylation, amprenavir (concentrations below 160 microM). This observation could be related to the behavior of fosamprenavir in the stomach. In the fasted state, gastric dissolution of fosamprenavir started immediately, resulting in a Cmax of 4 +/- 2 mM after 43 +/- 15 min; however, in the fed state, the fosamprenavir concentration remained below 20 microM for the first 90 min after drug intake. The postponed gastric dissolution may be attributed to a food-induced delay in tablet disintegration. CONCLUSION: For the first time, the pharmacokinetic profile of a drug was monitored in parallel with its gastrointestinal concentrations. The observed food effect in the plasma concentration-time profile of amprenavir after intake of its phosphate ester prodrug could be related to a food-induced delay in gastric dissolution of fosamprenavir.
Joachim Brouwers; Jan Tack; Patrick Augustijns
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-19
Journal Detail:
Title:  Pharmaceutical research     Volume:  24     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-11     Completed Date:  2007-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1862-9     Citation Subset:  IM    
Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Gasthuisberg O&N 2-Herestraat 49, box 921, Leuven, Belgium.
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MeSH Terms
Administration, Oral
Carbamates / administration & dosage,  blood,  chemistry,  pharmacokinetics*
Cross-Over Studies
Duodenum / metabolism*
Fasting / metabolism
Feasibility Studies
Food-Drug Interactions*
Gastric Juice / metabolism*
HIV Protease Inhibitors / administration & dosage,  blood,  chemistry,  pharmacokinetics*
Hydrogen-Ion Concentration
Intestinal Absorption*
Intestinal Secretions / metabolism*
Phosphoric Acid Esters / administration & dosage,  blood,  chemistry,  pharmacokinetics*
Postprandial Period
Sulfonamides / administration & dosage,  blood,  chemistry,  pharmacokinetics*
Reg. No./Substance:
0/Carbamates; 0/HIV Protease Inhibitors; 0/Phosphoric Acid Esters; 0/Sulfonamides; 0/Tablets; 0/fosamprenavir; 161814-49-9/amprenavir

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

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