Serum concentrations of gabapentin in cats with chronic kidney disease.

Abstract

OBJECTIVES: The purpose of this study was to assess serum concentrations of gabapentin in cats with chronic kidney disease (CKD) vs clinically healthy cats. METHODS: Five healthy cats were enrolled in a pharmacokinetic study. A single 20&#x2009;mg/kg dose of gabapentin was administered orally and blood was obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24 and 36&#x2009;h via a jugular catheter. Serum gabapentin concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Non-compartmental pharmacokinetic analysis was performed. The same five healthy cats plus 25 cats with stable International Renal Interest Society stage 2 (n&#x2009;=&#x2009;14) and 3 (n&#x2009;=&#x2009;11) CKD were enrolled in a limited sampling study. Cats in both groups received a single 10&#x2009;mg/kg dose of gabapentin, and serum gabapentin concentrations and compliance scores were obtained 3 and 8&#x2009;h post-administration. RESULTS: Cats with CKD had significantly higher dose-normalized serum gabapentin concentrations than normal cats at 3&#x2009;h (&#x2009;=&#x2009;0.0012 CKD vs normal 10&#x2009;mg/kg;&#x2009;=&#x2009;0.008 CKD vs normal 20&#x2009;mg/kg) and 8&#x2009;h (<0.0001 CKD vs normal 10&#x2009;mg/kg;<0.0001 CKD vs normal 20&#x2009;mg/kg). Both 3 and 8&#x2009;h dose-normalized serum gabapentin concentrations were significantly correlated with serum creatinine (3 h:&#x2009;=&#x2009;0.03,&#x2009;=&#x2009;0.39; 8&#x2009;h:&#x2009;=&#x2009;0.001,&#x2009;=&#x2009;0.57) and symmetric dimethylarginine (3&#x2009;h:&#x2009;=&#x2009;0.03,&#x2009;=&#x2009;0.41; 8&#x2009;h:&#x2009;=&#x2009;0.007,&#x2009;=&#x2009;0.48). There was a significant correlation between 3&#x2009;h serum gabapentin concentrations and compliance scores (&#x2009;=&#x2009;0.0002,&#x2009;=&#x2009;0.68). CONCLUSIONS AND RELEVANCE: Cats with CKD that received 10&#x2009;mg/kg of gabapentin had significantly higher dose-normalized serum concentrations than normal cats that received 20&#x2009;mg/kg, supporting the need to dose-reduce in this patient population.