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Pharmacokinetics and pharmacodynamics of long‐term continuous‐infusion doxorubicin
Author(s) -
Ackland Stephen P,
Ratain Mark J,
Vogelzang Nicholas J,
Choi Kyung E,
Ruane Maureen,
Sinkule Joseph A
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.39
Subject(s) - pharmacodynamics , doxorubicin , pharmacokinetics , medicine , leukopenia , pharmacology , nadir , steady state (chemistry) , continuous infusion , clinical pharmacology , chemotherapy , chemistry , satellite , engineering , aerospace engineering
Steady‐state plasma levels of doxorubicin and doxorubicinol were analyzed in 32 patients with advanced cancer, each of whom was given doxorubicin by long‐term continuous infusion at progressively increasing infusion rates. Patients received doxorubicin for 2 to 50 weeks at rates of 0.2 to 6.1 mg/m 2 /day. Dose‐limiting stomatitis and leukopenia were observed. The mean maximum steady‐state doxorubicin concentration was 6.04 ng/ml at a mean maximum infusion rate of 3.92 mg/m 2 /day. Clearance mechanisms did not appear to be saturated at the durations or infusion rates used in this study. The maximum steady‐state doxorubicin level and the In (initial WBC) were significant correlates of the In (nadir WBC) (p = 0.002 and 0.02, respectively). A model was constructed according to these two parameters that significantly describes In (nadir WBC) (p = 0.001). Neither age, infusion rate, nor doxorubicinol level correlated with nadir WBC. Stomatitis did not correlate with any of these parameters. The demonstration of this pharmacodynamic relationship highlights the potential importance of pharmacologic data collection in ongoing attempts to predict the clinical effects of anticancer drugs. Clinical Pharmacology and Therapeutics (1989) 45, 340–347; doi: 10.1038/clpt.1989.39