COMPARISON OF BODY-SURFACE AREA-BASED AND WEIGHT-BASED DOSAGE PROTOCOLS FOR DOXORUBICIN ADMINISTRATION IN DOGS

Pharmacokinetics and toxicity of a single dose of doxorubicin, at dosa ges of 30 mg/m(2) of body surface area and 1 mg/kg of body weight, wer e compared in 17 dogs. Effects of doxorubicin on complete blood cell c ount, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxor ubicin toxicosis at the 30-mg/m(2) dosage, revealed that 6 of 7 small dogs (less than or equal to 10 kg) became ill, whereas 7 of 10 large d ogs (> 10 kg) remained clinically normal. Small. dogs that received do xorubicin at a dosage of 30 mg/m(2) had higher peak plasma concentrati ons, greater area under the curve for plasma drug concentration vs tim e, longer drug elimination half-lives, greater volumes of distribution , and more clinical signs of toxicosis than had large dogs (P less tha n or equal to 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m(2) developed severe myelosuppression (< 1 x 10(3) granulocytes/mu l). In contrast to the toxicoses with body surface ar ea-based dosing. myelosuppression was not induced in small dogs that r eceived doxorubicin at a dosage of 1 mg/kg. In small and large dogs gi ven doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristic s and clinical signs of toxicosis were similar. Mean WBC counts and gr anulocyte counts for all dogs were lower on day 7 with 30 mg of doxoru bicin/ m(2) (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P less than or equal to 0.01). This study indicated that a body weight-based (milligram per kilogram) dosing regimen may result in mo re uniform therapeutic and toxic responses in dogs. Limited toxicosis was observed in dogs weighing > 10 kg treated with doxorubicin with ei ther dosing scheme; however, differences in pharmacokinetic profiles s uggested that 1 mg/kg may be an inappropriately low dosage.