title: Vincristine-induced neuropathy in the rat is not modified by drug-drug interactions with the P-glycoprotein inhibitor verapamil.
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 (99m)Tc-sestamibi in nervous tissue.
  
  
  RESULTS
  Quinidine (30 mg/kg) increased (99m)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.
  
  
  CONCLUSIONS
  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.
authors: Laboratoire de Toxicologie, Faculté de Pharmacie, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France. dbalayssac@chu-clermontferrand.fr
authors: David
authors: D
authors: Balayssac
authors: Anne
authors: A
authors: Cayre
authors: Bing
authors: B
authors: Ling
authors: Jean
authors: J
authors: Maublant
authors: Frederique
authors: F
authors: Penault-Llorca
authors: Alain
authors: A
authors: Eschalier
authors: François
authors: F
authors: Coudore
authors: Nicolas
authors: N
authors: Authier
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014750:Vincristine; D014700:Verapamil