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  • Title: Species differences in sirolimus stability in humans, rabbits, and rats.
    Author: Ferron GM, Jusko WJ.
    Journal: Drug Metab Dispos; 1998 Jan; 26(1):83-4. PubMed ID: 9443858.
    Abstract:
    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 degrees 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.
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