[Pharmacokinetics of doxorubicin alginate microspheres and evaluation of its hepatic arterial embolization in vivo].
OBJECTIVE
To investigate the pharmacokinetics of doxorubicin alginate microspheres (DOX-AM) in vivo after hepatic arterial embolization.


METHODS
China miniature pigs were chosen as the experimental animals. Transcatheter hepatic arterial chemoembolization (TACE) with DOX-AM (experimental group), lipiodol and DOX (DOX-lipiodol, control group 1), and infusion with DOX (control group 2) were performed after angiography and superselection of an intrahepatic branch of hepatic artery. After chemoembolization or infusion, the blood was collected at different time intervals. Drug concentration in plasma was measured by HLPC and the parameters of pharmacokinetics were calculated.


RESULTS
The values of T1/2, AUC, Cmax, and MRT of the DOX-AM were significantly different from those of control group 1 and control group 2. After embolization, the DOX-AM embolized in the vessel and still retained there at 8 weeks. The digital subtraction arteriography (DSA) and computerized tomography (CT) showed the reliable embolization results. The histological examination indicated that the liver damnifications were changed transitorily in all groups (P < 0.05) and were recovered within two weeks. The liver damnifications increased in following order: DOX < DOX-AM < DOX-lipiodol.


CONCLUSIONS
DOX-AM showed definite property of delayed release of drug in liver, and increased the retention time and concentration of DOX after embolization in vivo.
Liu
Dan
D
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Wang
Peng-cheng
PC
Qi
Xian-rong
XR
Zou
Qiang
Q
Zou
Ying-hua
YH
Hong
Hong
H
D000464:Alginates / Q000737:chemistry; D015901:Angiography, Digital Subtraction; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D016461:Chemoembolization, Therapeutic; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005260:Female; D006499:Hepatic Artery / Q000000981:diagnostic imaging / Q000378:metabolism*; D007459:Iodized Oil / Q000737:chemistry; D008099:Liver / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008863:Microspheres; D010316:Particle Size; D013552:Swine; D013556:Swine, Miniature; D014057:Tomography, X-Ray Computed
D000464:Alginates; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D007459:Iodized Oil; D004317:Doxorubicin