ISSN:
1573-0646
Keywords:
4′-deoxydoxorubicin
;
esorubicin
;
anthracycline
;
anticancer agent
;
pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The pharmacokinetics of esorubicin, a new anthracycline antibiotic, was investigated in conjunction with a phase I clinical trial. The drug was administered to 12 patients as an intravenous bolus at a dose of 20 to 40mg/m2. All patients had normal renal and hepatic functions and no third space fluid accumulation. Plasma and urine samples were assayed by HPLC. The peak plasma concentration of esorubicin was 0.74 ± 0.57 μM (mean ± SE). Esorubicin disappeared from plasma according to a tri-exponential pattern with a terminal half-life of 20.4 ± 7.3 hr. The area under the plasma concentration versus time curve was 0.64 ± 0.31 μMxhr. Total body plasma clearance was 45.5 ± 26.8 liter/min/m2 and the apparent volume of the central compartment, 41.0 ± 24.8 L. A single metabolite, 4′-deoxydoxorubicinol, was detected in plasma. This metabolite was observed in 5 patients only and its mean peak concentration was 0.029 ± 0.017 μM. The area under the plasma versus concentration time curve for 4′-deoxydoxorubicinol was 0.02 ± 0.014 μMxhr. The urinary excretion of total fluorescence within 5 days of therapy was 7.3 ± 1.3% of the administered dose. Esorubicin represented more than 80% of the excreted anthracyclines. As in plasma, 4′ -deoxydoxorubicinol was the only metabolite detectable in urine. No correlation between the various pharmacokinetic parameters and drug-induced toxicity was observed in this small group of patients.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00170759
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