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  • Title: Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function.
    Author: Benjamin RS, Riggs CE, Bachur NR.
    Journal: Cancer Res; 1977 May; 37(5):1416-20. PubMed ID: 856462.
    Abstract:
    A new, nondestructive, plasma extraction technique ultilizing chloroform:isopropyl alcohol (1:1) and ammonium sulfate saturation has been devised to isolate adriamycin and its metabolites from human plasma. Adriamycin was the most prominent species in plasma. It disappeared according to a triphasic pattern with a mean half-life of 30 hr. Six metabolites have been clearly separated from adriamycin by thin-layer chromatography. Three were aglycones and three were polar metabolites, one of which has been identified as adriamycinol. All metabolites appeared rapidly in plasma and disappeared according to a biphasic or tri-phasic pattern. The polar metabolites in plasma were found in similar relative concentration to those in urine. In contrast to the small Quantities of aglycones in urine, however, significant concentrations of aglycones were found in plasma. The least prominent metabolite was adriamycin aglycone; the most prominent metabolite was a less polar aglycone, most likely deoxyadriamycin aglycone, and a more polar aglycone, presumably demethyl deoxyadriamycinol aglycone, was the only metabolite to show variable pharmacokinetics in different patients. The nondestructive plasma extraction technique has verified the presence of extensive human metabolism of adriamycin and demonstrated the presence of aglycone and polar metabolites.
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