TY - JOUR
T1 - Dose-dependent pharmacokinetics of flavone acetic acid in mice
AU - Damia, Giovanna
AU - Zanette, Maria Luisa
AU - Rossi, Cosmo
AU - Mandelli, Rosella
AU - Ferrari, Aurora
AU - D'Incalci, Maurizio
PY - 1988/7
Y1 - 1988/7
N2 - The pharmacokinetics of the novel anticancer agent, flavone acetic acid (FAA) were investigated in Balb-c mice treated with i. v. doses of 100 mg/kg or 300 mg/kg, using an HPLC assay. The kinetics of disappearance from plasma was monoexponential and dose-dependent. After 100 mg/kg, the plasma peak level was 250±11 μg/ml, t1/2 was 0.5 h, and AUC was 309 μg/ml per h. After 300 mg/kg, the plasma peak level was 710±57 μg/ml, t1/2 was 2.1 h, and the area under the curve (AUC) 1771 μg/ml h. Mouse plasma protein binding of FAA was about 70%. As is the case with plasma, in all tissues analyzed, the FAA-AUC values were disproportinately greater after 300 mg/kg than after 100 mg/kg. The highest drug concentrations were found in the liver and small intestine; concentrations were intermediate in lung, heart, and spleen, and lowest in brain. Less than 5% of the FAA dose was eliminated as unchanged drug in the stool. Total excretion of FAA as unchanged drug in the urine collected up to 96 h after drug treatment corresponded to 75% and 60% of the i. v. doses of 100 and 300 mg/kg, respectively. A minor fraction of FAA dose, corresponding to 1% and 6% of the two doses, was eliminated in the urine as a FAA glucuronide or sulfate.
AB - The pharmacokinetics of the novel anticancer agent, flavone acetic acid (FAA) were investigated in Balb-c mice treated with i. v. doses of 100 mg/kg or 300 mg/kg, using an HPLC assay. The kinetics of disappearance from plasma was monoexponential and dose-dependent. After 100 mg/kg, the plasma peak level was 250±11 μg/ml, t1/2 was 0.5 h, and AUC was 309 μg/ml per h. After 300 mg/kg, the plasma peak level was 710±57 μg/ml, t1/2 was 2.1 h, and the area under the curve (AUC) 1771 μg/ml h. Mouse plasma protein binding of FAA was about 70%. As is the case with plasma, in all tissues analyzed, the FAA-AUC values were disproportinately greater after 300 mg/kg than after 100 mg/kg. The highest drug concentrations were found in the liver and small intestine; concentrations were intermediate in lung, heart, and spleen, and lowest in brain. Less than 5% of the FAA dose was eliminated as unchanged drug in the stool. Total excretion of FAA as unchanged drug in the urine collected up to 96 h after drug treatment corresponded to 75% and 60% of the i. v. doses of 100 and 300 mg/kg, respectively. A minor fraction of FAA dose, corresponding to 1% and 6% of the two doses, was eliminated in the urine as a FAA glucuronide or sulfate.
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U2 - 10.1007/BF00254180
DO - 10.1007/BF00254180
M3 - Article
C2 - 3396145
AN - SCOPUS:0023734029
VL - 22
SP - 47
EP - 50
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 1
ER -