Pharmacokinetics and metabolism of pirarubicin in humans: correlation with pharmacodynamics.
The pharmacokinetic monitoring of anthracycline-containing regimens is warranted because of the important toxicity of these drugs and because pharmacokinetic-pharmacodynamic relationships have been clearly established. We studied the pharmacokinetics of the new anthracycline pirarubicin in 80 courses of treatment performed in 27 patients, using a limited sampling protocol we had previously validated. We observed (for 47 of these courses) a significant correlation between the leucocyte cell kill and the pirarubicin area under the time x concentration curve, but the most significant correlation was obtained using the plasma concentration of doxorubicin, a metabolite of pirarubicin, at the end of the infusion. On the basis of this value, it is possible to predict for pirarubicin haematological toxicity in a way that can help the clinician in identifying patients at risk for toxicity.
Marchiset-Leca
D
D
Laboratoire de Pharmacocinétique, Centre Hospitalier Départemental de Castelluccio, Ajaccio, France.
Leca
F R
FR
Galeani
A
A
Noble
A
A
Catalin
J
J
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006207:Half-Life; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D015203:Reproducibility of Results
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C027260:pirarubicin