[Development of an individualized therapy for establishing the optimal dosage by the pharmacokinetics profiles of anticancer agents].
Therapeutic drug monitoring (TDM) is widely applied to a variety of medications, including antibiotics, immunosuppressants, and antidepressants, but the clinical utility of TDM for anticancer agents is currently limited by several factors. The primary reason is the poorly-defined concentration-effect relationships for most anticancer drugs. TDM has the potential to improve the clinical use of anticancer agents. This paper reviews the relations between the pharmacokinetics of a new anticancer agent, amrubicin, and the clinical response and toxic side effects in patients. The plasma concentration of amrubicin peaked immediately after a bolus intravenous injection of the drug and declined in a biexponential manner thereafter, whereas that of C-13 hydroxy metabolite amrubicinol also peaked just after amrubicin injection but decreased more gradually compared with that of amrubicin. The apparent total clearance of amrubicin showed a large interindividual variability, despite adjustment of dosage for body surface area. Leukocytopenia of grades 3 or 4 occurred in most patients, and thrombocytopenia and anemia of grades 3 or 4 were also common. Since the area-under the curves of amrubicin and amrubicinol seemed to be associated with the severity of hematological toxicities, it is thought that the plasma concentration of amrubicin and amrubicinol may provide useful information for establishing the optimal dosage of amrubicin in each patient.
Hamada
Akinobu
A
Department of Pharmacy, Kumamoto University Hospital, Japan. ahamada@kaiju.medic.kumamoto-u.ac.jp
D000368:Aged; D000740:Anemia / Q000139:chemically induced; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001830:Body Surface Area; D016903:Drug Monitoring; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced
D018943:Anthracyclines; D000970:Antineoplastic Agents; C055866:amrubicin