Unchanged pharmacokinetics of etoposide given by intra-arterial hepatic infusion as compared with i.v. infusion |
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Authors: | O van Tellingen Maarten T Kuck L T Vlasveld Sjoerd Rodenhuis Willem J Nooijen Jos H Beijnen |
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Institution: | (1) Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands, NL;(2) Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam, The Netherlands, NL;(3) Department of Pharmacy, Slotervaartziekenhuis, Amsterdam, The Netherlands, NL |
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Abstract: | We investigated the pharmacokinetics of etoposide given to a patient suffering from multifocal liver metastases from an unknown
primary tumor. The drug was given either by i.v. infusion or by hepatic arterial infusion (HAI). The calculated pharmacokinetic
parameters (mean values ± SD) were similar after i.v. infusion and HAI, viz., 6.4±0.7 versus 6.5±0.2 h for the terminal elimination
half-life (t
1/2β), 98.5±1.3 versus 101.3±5.9 mg l-1 h for the area under the plasma concentration-time curve (AUC), 21.2±0.3 versus 20.6±1.2 ml min-1 m-2 for clearance (Cl), 17.7±1.9 versus 18.1±2.6 mg/l for the peak concentration, and 11.7±1.3 versus 11.6±1.0 l/m2 for the volume of distribution (V
d
), respectively. We therefore conclude that administration of etoposide by HAI does not result in a significantly higher liver
extraction. Hepatic extraction of etoposide is determined by the fraction of non-protein-bound (free) drug present. The lack
of a difference between the two administration routes suggests that under in vivo conditions the equilibrium between free
and bound drug is established before the drug reaches the hepatic arterioles. Consequently, administration by HAI does not
lead to an increased exposure of the tumor in the liver to free (active) etoposide. Furthermore, the overall exposure of the
liver to total (bound + free) etoposide is increased only from about 100 to 120 mg l-1 h. These results do not favor the use of this more complex route of drug administration in the treatment of (metastatic)
cancer located in the liver.
Received: 5 November 1995/Accepted: 17 January 1996 |
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Keywords: | Etoposide Intra-arterial infusion Liver Pharmacokinetics |
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