Pharmacokinetics of adriamycin, adriamycinol, and antipyrine in patients with moderate tumor involvement of the liver.
The pharmacokinetics of adriamycin, its metabolite adriamycinol, and antipyrine were studied in 17 patients with moderate tumor involvement of the liver and compared to that of 19 tumor patients with normal liver function (Preiss et al. 1985). The individual liver function parameters deviated from normal by a factor ranging from 2.5 to 12.2. The t1/2 alpha and t1/2 beta, the AUC (corrected for body weight and dose) and the total body clearance (CL, corrected for body weight) of adriamycin did not differ significantly between the two groups of patients. Likewise, there was no difference in the kinetic parameters of antipyrine between the two groups. Unlike adriamycin and antipyrine, adriamycinol was found to have a significantly longer t1/2term (60.5 vs 28.3 h, P less than 0.001), an increased AUC (3.00 vs 1.43 h/ug per ml, P less than 0.02), and a higher AUCadriamycinol/AUCadriamycin ratio (0.94 vs 0.52, P less than 0.02) in patients with moderate tumor involvement of the liver. The CL, the AUC, and t1/2 beta of adriamycin correlated significantly (P less than 0.001 and P less than 0.01) with the corresponding kinetic parameters of antipyrine, but not with the usual liver function parameters. No correlation could be found between the kinetic parameters of adriamycinol and those of antipyrine.
Preiss
R
R
Department of Clinical Pharmacology, Charité Humboldt University, Berlin, German Democratic Republic.
Matthias
M
M
Sohr
R
R
Brockmann
B
B
Hüller
H
H
D000328:Adult; D000983:Antipyrine / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D004317:Doxorubicin; C010013:adriamycinol; D000983:Antipyrine