Pharmacokinetic evaluation of percutaneous hepatic venous isolation for administration of regional chemotherapy

Hepatic artery infusion (HAI) chemotherapy has been used to treat patients with unresectable liver tumours. We report a preclinical study of the pharmacokinetics of HAI combined with hepatic venous drug extraction (HVDE) for regional administration of doxorubicin. HVDE was aided by a double balloon...

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Bibliographic Details
Published in:Surgical oncology 1995-08, Vol.4 (4), p.205-216
Main Authors: August, D.A., Verma, N., Vaerten, M.A., Shah, R., Andrews, J.C., Brenner, D.E.
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
Female
Hepatic Artery
Hepatic Veins
Infusions, Intra-Arterial - methods
Liver - metabolism
liver tumours
pharmacokinetics
regional chemotherapy
Swine
Tissue Distribution
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Summary:Hepatic artery infusion (HAI) chemotherapy has been used to treat patients with unresectable liver tumours. We report a preclinical study of the pharmacokinetics of HAI combined with hepatic venous drug extraction (HVDE) for regional administration of doxorubicin. HVDE was aided by a double balloon catheter inserted via femoral vein cutdown into the inferior vena cava to collect all hepatic vein blood. Pigs received doxorubicin 0.5–9.0 mg kg −1 over 90 min via HAI or systemic infusion (SYSI). HVDE was performed for 240 min. SYSI pigs underwent hepatic venous isolation without drug filtration. Doxorubicin levels were assayed using high-pressure liquid chromatography (HPLC). HAI/HVDE reduced systemic exposure to doxorubicin with equivalent hepatic exposure at all doses. Pharmacokinetic enhancement ranged from 7.0 to 22.3 for peak concentration, 8.8–23.2 for the area under the curve and 2.9–4.2 for tissue concentration. HAI/HVDE also prevented the mortality which was observed with SYSI administration of high-dose (5.0 and 9.0 mg kg −1) doxorubicin. We conclude that HAI/HVDE reduces systemic exposure to doxorubicin as compared with SYSI of equivalent doses. Pharmacokinetic enhancement indices suggest that HAI/HVDE may allow equivalent hepatic drug exposure with reduced systemic exposure. This method may be applicable to other drugs and to other anatomic settings in which enhanced regional drug delivery is desirable.
ISSN:0960-7404
1879-3320
DOI:10.1016/S0960-7404(10)80037-4