Pharmacokinetics of doxorubicin in man: dose and schedule dependence.
Doxorubicin serum elimination kinetics were measured by HPLC in three different patient groups. A dose of (a) 30 mg/m2; (b) 50 mg/m2, and (c) 4 x 15 mg/m2 every 10 h was administered by bolus injection to (a) 10, (b) 6, and (c) 8 patients. The results obtained provided strong evidence for a nonlinear dependence of doxorubicin serum elimination on the dose and administration schedule used. Comparing the 15 and 30 mg/m2 dose there was no significant increase in early drug levels but a marked increase in terminal half-life. At doses higher than 30 mg/m2, however, there was a steep increase in early drug levels, too. Moreover a marked cumulation of the anthracycline in the central compartment following short-term (4 x 15 mg/m2 every 10 h) consecutive administration was found. To obtain an optimal concentration x time product by single bolus injection a dose equal or higher than 30 mg/m2 should be used. However, in this dose range a steep dose-dependent rise in early drug levels is to be expected. As early high serum levels correlate with congestive heart failure, administration schedules reaching effective concentration x time products without high peak levels such as continuous infusion or consecutive administration of low doses seem to be necessary.
Erttmann
R
R
Department of Pediatric Oncology, Children's Hospital, University of Hamburg, Federal Republic of Germany.
Erb
N
N
Steinhoff
A
A
Landbeck
G
G
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D004317:Doxorubicin