EVIDENCE OF POSSIBLE DOSE-DEPENDENT DOXORUBICIN PLASMA KINETICS IN MAN

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 67  (1) , 63-69
Abstract
The published plasma clearance profiles of [the antineoplastic drug] doxorubicin in man (with differing liver status) were analyzed further using a kinetic model instead of a linear regression model. At high (60 mg/m2 and 45 mg/m2) and intermediate (30 mg/m2) doxorubicin dose levels, a triphasic drug clearance pattern is apparent. At a low dose level (15 mg/m2), a biphasic profile can adequately describe the kinetics. This association of the kinetics with drug dose was demonstrated in several ways (the simplest of which involves graphic overlaying of juxtaposed plasma clearances), and shows the emergence of a kinetic profile for low dose levels that is markedly different from that at high dose levels. At doses greater than .apprx. 45 mg/m2, a probable saturation of response mechanisms is observed. It is not possible to interpret these results in terms of pure dose-dependent responses because of the varying health status of the individual subjects between and within experimental treatment.