Vincristine-Induced Neuropathy in the Rat Is Not Modified by Drug-Drug Interactions with the P-Glycoprotein Inhibitor Verapamil
| Autor: | David Balayssac, Nicolas Authier, Frédérique Penault-Llorca, Alain Eschalier, Jean Maublant, Bing Ling, François Coudoré, Anne Cayre |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Drug Vincristine media_common.quotation_subject ATP-binding cassette transporter Pharmacology Rats Sprague-Dawley Drug Discovery medicine Animals Drug Interactions Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 media_common P-glycoprotein P-glycoprotein Inhibitor biology business.industry Body Weight fungi food and beverages Cancer General Medicine medicine.disease Rats Infectious Diseases medicine.anatomical_structure Verapamil Oncology Peripheral nervous system biology.protein Nervous System Diseases business medicine.drug |
| Zdroj: | Chemotherapy. 54:336-342 |
| ISSN: | 1421-9794 0009-3157 |
| DOI: | 10.1159/000151540 |
| Popis: | 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 99mTc-sestamibi in nervous tissue. Results: Quinidine (30 mg/kg) increased 99mTc-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. |
| Databáze: | OpenAIRE |
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