Abstract
The pharmacokinetics of 5-fluorouracil (5FU) following its administration via the hepatic artery in conjunction with biodegradable albumin microspheres and angiotensin II have been studied. Peripheral venous concentrations of 5FU are lower and plasma clearance values higher following intrahepatic arterial administration compared with a similar dose administered by intravenous infusion over both 2 h and 24 h. For the 2 h drug infusions, plasma 5FU concentrations following co-treatment with angiotensin II and microspheres via the hepatic artery were intermediate between those of arterial and venous infusions of 5FU alone. There was a trend towards the peak plasma drug concentrations and the area under the plasma concentration-time curve (AUC) being significantly lower following co-treatment with angiotensin II and microspheres compared with intra-arterial and intravenous infusions of 5FU over 24 h. Co-administration of 5FU, angiotensin II and microspheres via the hepatic artery may reduce drug exposure in the systemic compartment and therefore may increase the therapeutic ratio of 5FU administration via the hepatic artery.
Highlights
MethodsSeven patients with advanced colorectal hepatic metastases and indwelling hepatic arterial perfusion catheters were studied
Systemic chemotherapy for colorectal hepatic metastases is associated with high toxicity and poor therapeutic outcome
There is a lack of data supporting its efficacy in prolonging survival (Malik et al, 1988), the popularity of regional chemotherapy for neoplastic liver disease is continuing to gather momentum
Summary
Seven patients with advanced colorectal hepatic metastases and indwelling hepatic arterial perfusion catheters were studied. Estimations of the percentage of hepatic replacement of liver parechyma by tumour were based on 99'Tc tin colloid imaging performed before the study. Baseline shunting was estimated for each patient on two separate occasions before commencing the present study (Goldberg et al, 1987b). Pharmacokinetic studies were performed for each of the treatments listed. (b) Intrahepatic arterial infusion of I g of 5FU over 24 h. I.a. All; AMS; 5FU: (a) Intrahepatic arterial infusion of angiotensin II (AII) 10 iLg min-' for 100 s, bolus injection of albumin microspheres 300 mg (AMS), infusion of 5FU, 30 mg kg-' over 2 h. (b) Intrahepatic arterial infusion of angiotensin II (AII) 1l0tg min-' for 100 s, bolus injection of albumin microspheres (AMS), infusion of 5FU, 1 g over 24 h All; AMS; 5FU: (a) Intrahepatic arterial infusion of angiotensin II (AII) 10 iLg min-' for 100 s, bolus injection of albumin microspheres 300 mg (AMS), infusion of 5FU, 30 mg kg-' over 2 h. (b) Intrahepatic arterial infusion of angiotensin II (AII) 1l0tg min-' for 100 s, bolus injection of albumin microspheres (AMS), infusion of 5FU, 1 g over 24 h
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