Doxorubicin pharmacokinetics—The effects of protein deprivation

Abstract

Recent studies suggest that protein-calorie malnutrition decreases tumor response to chemotherapy. This study was designed to evaluate the effects of dietary protein deprivation on the pharmacokinetics and distribution of Adriamycin. Male Sprague-Dawley rats were assigned randomly to receive either in a regular diet or a high-carbohydrate, protein-free diet for the duration of the experiment. Ten days after the initiation of the designated diet, all animals received a single dose (5.0 mg/kg) of Adriamycin intravenously. Animals were sacrificed at 0.5, 1.2, 6, 24, and 48 hr following drug administration, and the concentration of Adriamycin in serum, urine, and tissue was determined by fluorometric assay. Animals maintained on the regular diet continued to gain weight during the study interval, while animals provided the protein-free diet lost an average of 21% of their initial study weight ( P < 0.01). Serum Adriamycin concentration was significantly lower in the protein-free diet animals at 0.5, 1, 2, 24, and 48 hr following administration: Adriamycin was not detectable in the serum of the protein-free diet animals at 48 hr, but was still present in the serum of the regular diet group ( P < 0.01). The cumulative urinary excretion of Adriamycin, expressed as a percentage of the administered dose, was identical in both dietary groups during the initial 24 hr, but was significantly higher in the protein-free diet group by 48 hr after administration ( P < 0.05). Significant differences were observed when liver, kidney, lung, and heart Adriamycin concentrations were compared. The elevated concentration of Adriamycin in the kidneys of the protein-free diet animals correlated with the increased urinary drug excretion, and indicated that accelerated renal clearance of Adriamycin was one possible mechanism for the more rapid serum elimination of the drug in the protein-free diet animals.