Doxorubicin pharmacokinetics: the effect of abnormal liver biochemistry tests.
We studied variability in doxorubicin pharmacokinetics in 24 patients with abnormal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography. The relationship between doxorubicin clearance (dose/AUC) and liver biochemistry tests (AST, bilirubin, albumin, alkaline phosphatase and indocyanine green clearance) was investigated. Patients with a raised bilirubin level had reduced doxorubicin clearance, but there was no clear relationship between the extent of this elevation and the reduction in doxorubicin clearance. Doxorubicin clearance was lower in patients with an isolated increase in AST than in those with normal liver biochemistry, but this difference was not statistically significant. Nevertheless, there was a significant correlation between reduced doxorubicin clearance and both raised serum AST levels and low indocyanine green clearance. These pharmacokinetic data suggest that current dose reductions based solely on the extent to which bilirubin is elevated may not be optimal.
Imperial Cancer Research Fund Clinical Oncology Unit, United Medical and Dental Schools, Guy's Hospital, London, UK.
C J
CJ
Twelves
N A
NA
Dobbs
H C
HC
Gillies
C A
CA
James
R D
RD
Rubens
P G
PG
Harper
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D007208:Indocyanine Green / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; D004317:Doxorubicin; D001219:Aspartate Aminotransferases; D007208:Indocyanine Green; D001663:Bilirubin