The effect of a high‐fat meal on the oral bioavailability of the immunosuppressant sirolimus (rapamycin)
JJ Zimmerman, GM Ferron, HK Lim… - The Journal of Clinical …, 1999 - Wiley Online Library
JJ Zimmerman, GM Ferron, HK Lim, V Parker
The Journal of Clinical Pharmacology, 1999•Wiley Online LibraryThe 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 …
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 …
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 intra‐subject 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.
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