“Increased toxicity of P-glycoprotein-substrate chemotherapeutic agents in a dog with the MDR1 deletion mutation associated with ivermectin sensitivity”

Katrina L. Mealey et al.

J Am Vet Med Assoc. 2003 Nov 15;223(10):1453-5

A 4yr FS collie was diagnosed with World Health Organization stage IVb lymphoma.  She experienced side effects from her treatment.  Because the dog developed myelosuppression and signs of  gastrointestinal tract toxicosis after treatment with P-glycoprotein-substrate chemotherapeutic agents (ie, vincristine, doxorubicin, and vinblastine), but not after treatment with a non-P-glycoprotein-substrate drug (cyclophosphamide), a functional defect in P-glycoprotein was suspected. PCR testing revealed the dog was heterozygous for the mutation. 

“The pharmacokinetics of cytarabine in dogs when administered via subcutaneous and continuous intravenous infusion routes.”

Crook, Early, Messenger, Munana, Gallagher, Papich

J Vet Pharmacol Therap. 36, 408-411

A cross-over study comparing 50mg/kg SQ twice daily for two days (200mg/kg over 2 days) versus 25mg/kg/hour IV infusion (200mg/kg over 8 hours). Blood values are speculated to reflect BBB transition of the drug for effectiveness (more important than CSF levels). The ability to achieve and maintain a steady-state is proposed to be necessary for the most effective transfer across the BBB. This was achievable with IV infusion but not the SQ administration protocol.