Document Detail

The effect of a high-fat meal on the oral bioavailability of the immunosuppressant sirolimus (rapamycin).
MedLine Citation:
PMID:  10579146     Owner:  NLM     Status:  MEDLINE    
The bioavailability of an oral nonaqueous solution of sirolimus was compared under fasting conditions and after a high-fat meal in a randomized, two-way crossover pharmacokinetic study. Healthy volunteers were administered a 15 mg single dose of sirolimus on two occasions, once while fasting and once after consumption of a high-fat breakfast. Whole blood concentrations of sirolimus were assayed by using a validated method with high-performance liquid chromatography/tandem mass spectrometric detection. Sirolimus was absorbed more slowly when administered after a high-fat meal than when administered after fasting, as shown by statistically significant reductions in peak concentration (Cmax) and the ratio of Cmax to the area under the curve (AUC), and lengthening of the time to peak concentration. The oral availability of sirolimus was increased to a modest extent (35%) and in a uniform manner when administered with a high-fat meal; the geometric mean ratio of the fed/fasting AUC values was 1.35, with a 90% confidence interval of 1.26 to 1.46. Food had no effect on the terminal half-life of sirolimus (mean values of 67 to 68 hours). The 35% increase in AUC obtained after a high-fat meal appears small relative to the intersubject and intrasubject variabilities observed in clinical trials. However, to minimize unnecessary fluctuations in trough whole blood sirolimus concentrations, it is advisable that sirolimus be administered consistently in individual patients, either with or without meals.
J J Zimmerman; G M Ferron; H K Lim; V Parker
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  39     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-16     Completed Date:  1999-12-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1155-61     Citation Subset:  IM    
Clinical Pharmacokinetics Department, Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101-2528, USA.
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MeSH Terms
Biological Availability
Cross-Over Studies
Dietary Fats / pharmacology*
Food-Drug Interactions
Gas Chromatography-Mass Spectrometry
Immunosuppressive Agents / blood,  pharmacokinetics*
Patient Dropouts
Sirolimus / blood,  pharmacokinetics*
Time Factors
Reg. No./Substance:
0/Dietary Fats; 0/Immunosuppressive Agents; 53123-88-9/Sirolimus

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

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