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 dosages of 30 mg/m2 of body surface area and 1 mg/kg of body weight, were compared in 17 dogs. Effects of doxorubicin on complete blood cell count, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxorubicin toxicosis at the 30-mg/m2 dosage, revealed that 6 of 7 small dogs (< or = 10 kg) became ill, whereas 7 of 10 large dogs (> 10 kg) remained clinically normal. Small dogs that received doxorubicin at a dosage of 30 mg/m2 had higher peak plasma concentrations, greater area under the curve for plasma drug concentration vs time, longer drug elimination half-lives, greater volumes of distribution, and more clinical signs of toxicosis than had large dogs (P < or = 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m2 developed severe myelosuppression (< 1 x 10(3) granulocytes/microliters). In contrast to the toxicoses with body surface area-based dosing, myelosuppression was not induced in small dogs that received doxorubicin at a dosage of 1 mg/kg. In small and large dogs given doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristics and clinical signs of toxicosis were similar. Mean WBC counts and granulocyte counts for all dogs were lower on day 7 with 30 mg of doxorubicin/m2 (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Arrington
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Department of Urban Practice, University of Tennessee, College of Veterinary Medicine, Knoxville 37901-1071.
Legendre
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Tabeling
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Frazier
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D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001830:Body Surface Area; D001835:Body Weight; D004285:Dogs / Q000033:anatomy & histology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects
D004317:Doxorubicin