PT - JOURNAL ARTICLE AU - Geraldine M. Ferron AU - William J. Jusko TI - Species Differences in Sirolimus Stability in Humans, Rabbits, and Rats DP - 1998 Jan 01 TA - Drug Metabolism and Disposition PG - 83--84 VI - 26 IP - 1 4099 - http://dmd.aspetjournals.org/content/26/1/83.short 4100 - http://dmd.aspetjournals.org/content/26/1/83.full SO - Drug Metab Dispos1998 Jan 01; 26 AB - Species differences in the in vitro stability of sirolimus was assessed in plasma and whole blood in relation to red blood cell distribution. Fresh blood and plasma samples obtained from humans, rabbits, and rats were aliquoted and spiked with sirolimus. After incubation from 0 to 144 hr in a shaking water bath maintained at 37°C, sirolimus concentrations were quantified by a specific high-liquid performance chromatographic method. Sirolimus was unstable in both plasma and whole blood. Sirolimus degradation half-life in whole blood was 135 hr (vs. 7.2 hr in plasma) in humans, 62 hr (vs. 3.1 hr) in rabbits, and 15 hr (vs. 2.2 hr) in rats. Sirolimus stability is greater in whole blood compared with plasma in proportion to the whole blood/plasma ratio and hematocrit. In vivo instability may account for up to 36% of sirolimus clearance in humans and 13% in rabbits, and this is an important factor in the pharmacokinetics of this drug. The American Society for Pharmacology and Experimental Therapeutics