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Vincristine-Induced Neuropathy in the Rat Is Not Modified by Drug-Drug Interactions with the P-Glycoprotein Inhibitor Verapamil

Vincristine-Induced Neuropathy in the Rat Is Not Modified by Drug-Drug Interactions with the... Background: Cancer patients can be exposed to drug interactions during treatment with toxic anticancer drugs. The peripheral nervous system is a target for neurotoxic anticancer drugs. P-glycoprotein is essential for the functional integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible drug interactions could lead to adverse neurotoxic reactions. Methods: In a rat model of vincristine-induced neuropathy, we assessed the consequences of potential drug interactions of vincristine with some P-glycoprotein-inhibiting drugs, chosen because of their potency to increase the incorporation of <sup>99m</sup>Tc-sestamibi in nervous tissue. Results: Quinidine (30 mg/kg) increased <sup>99m</sup>Tc-sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats. Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG and sciatic nerve. Combination treatment with the verapamil-vincristine regimen had a tendency to lower weight gain and altered nociceptive thresholds of neuropathic animals. Conclusion: Behavioral pain tests did not reveal an increase in vincristine neurotoxicity following combination treatment with verapamil and vincristine. This regimen only led to a slight increase in general toxicity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemotherapy Karger

Vincristine-Induced Neuropathy in the Rat Is Not Modified by Drug-Drug Interactions with the P-Glycoprotein Inhibitor Verapamil

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References (32)

Publisher
Karger
Copyright
© 2008 S. Karger AG, Basel
ISSN
0009-3157
eISSN
1421-9794
DOI
10.1159/000151540
Publisher site
See Article on Publisher Site

Abstract

Background: Cancer patients can be exposed to drug interactions during treatment with toxic anticancer drugs. The peripheral nervous system is a target for neurotoxic anticancer drugs. P-glycoprotein is essential for the functional integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible drug interactions could lead to adverse neurotoxic reactions. Methods: In a rat model of vincristine-induced neuropathy, we assessed the consequences of potential drug interactions of vincristine with some P-glycoprotein-inhibiting drugs, chosen because of their potency to increase the incorporation of <sup>99m</sup>Tc-sestamibi in nervous tissue. Results: Quinidine (30 mg/kg) increased <sup>99m</sup>Tc-sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats. Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG and sciatic nerve. Combination treatment with the verapamil-vincristine regimen had a tendency to lower weight gain and altered nociceptive thresholds of neuropathic animals. Conclusion: Behavioral pain tests did not reveal an increase in vincristine neurotoxicity following combination treatment with verapamil and vincristine. This regimen only led to a slight increase in general toxicity.

Journal

ChemotherapyKarger

Published: Jan 1, 2008

Keywords: Verapamil; Vincristine; Drug-drug interactions; Neuropathy; P-glycoprotein; 99m Tc-Sestamibi

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