Objective—To determine whether antiepileptic drugs (AEDs) are substrates for canine P-glycoprotein (P-gp).
Sample Population—OS2.4/Doxo cells (canine osteosarcoma cells induced via exposure to doxorubicin to highly express P-gp).
Procedures—Competitive inhibition of rhodamine 123 efflux from OS2.4/Doxo cells was used to determine whether AEDs were substrates for canine P-gp. Flow cytometry was used to quantify mean fluorescence intensity of cells treated with rhodamine alone and in combination with each experimental drug.
Results—Known P-gp substrate drugs ivermectin and cyclosporin A altered rhodamine efflux by 90% and 95%, respectively. Experimental drugs altered rhodamine efflux weakly (diazepam, gabapentin, lamotrigine, levetiracetam, and phenobarbital) or not at all (carbamazepine, felbamate, phenytoin, topirimate, and zonisamide).
Conclusions and Clinical Relevance—At clinically relevant doses, it appeared that AEDs were weak substrates (diazepam, gabapentin, lamotrigine, levetiracetam, and phenobarbital) or were not substrates (carbamazepine, felbamate, phenytoin, topirimate, and zonisamide) for canine P-gp. Therefore, it seems unlikely that efficacy of these AEDs is affected by P-gp expression at the blood-brain barrier in dogs.
CASE DESCRIPTION A5.5-year-old sexually intact male Bull Terrier was referred for evaluation because of sudden facial swelling and an inability to close its mouth.
CLINICAL FINDINGS Physical examination revealed bilaterally elevated nictitating membranes, an inability to adduct the mandible without assistance, and severe, diffuse, firm masticatory muscle swelling. Computed tomographic examination of the head revealed symmetric bilateral enlargement of the temporalis, masseter, and pterygoid muscles with heterogeneous contrast enhancement. Intracompartmental pressures in the left and right temporalis muscles as measured with an invasive arterial blood pressure transducer were 72 and 96 mm Hg, respectively.
TREATMENT AND OUTCOME Emergent fasciotomy of the temporalis and masseter muscles was performed, followed by medical management with corticosteroids and analgesics. The diffuse facial swelling resolved within 1 week after surgery. Results of serologic testing for antibody against masticatory 2M muscle fibers were negative. Results of histologic examination of temporalis muscle specimens were consistent with mild to moderate multifocal neutrophilic and histiocytic myositis with myofiber degeneration and necrosis.
CLINICAL RELEVANCE Acute compartmental syndrome should be considered as a differential diagnosis for dogs with a sudden onset of severe skeletal muscle swelling, signs of pain, and dysfunction. Findings for this dog with acute compartmental syndrome isolated to the masticatory muscles suggested that emergent fasciotomy followed by medical management may be an effective technique for treatment of this rare disease in dogs.