COMPARISON OF THE PHARMACOKINETICS OF MULTIPLE AND SINGLE DOSE ADMINISTRATIONS OF ADRIAMYCIN

Adriamycin (ADR) to a total dose of 11 mg/kg LD 10 60) was administered intraperitoneally to female Balb/cKa mice either as a single dose or in multiple dose fractions. The concentration of ADR equivalents as a function of time after injection was determined using a fluorometric assay in the heart, lung, liver, kidney and intramuscularly growing EMT-6/Ro tumor. The results for single doses indicate both the maximum attainable tissue drug level and retention kinetics to be tissue specific. At 1-3 hr post-injection, measured values were highest in the liver and lowest in the tumor. Adriamycin equivalents had a longer half-life (t 1 2) in the tumor (67 hr) than in the other tissues examined: lung, (45 hr), liver (29 hr), kidney (27 hr), and heart (20 hr). Studies also were performed to determine whether the ADR pharmacokinetics are altered during a multiple dose regimen. Mice were given either a single dose of 5.5 mg/kg, 2 daily doses of 2.75 mg/kg, or 5 daily doses of 1.1 mg/kg. The results showed: 1) a build-up in tissue ADR equivalents with a maximum value after each fraction dependent solely on the level of drug remaining from the previous dose and 2) that in all tissues studied, the pharmacokinetics of the subsequent dose of ADR are unaffected by both the size and number of previous dose increments. © 1979.