Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats

Abstract

Trazodone and gabapentin are common oral sedatives in cats, used alone or combined, but no pharmacokinetic studies exist for trazodone in this species. The objective of this study was to determine the pharmacokinetics of oral trazodone (T) alone, or in combination with gabapentin (G) in healthy cats. Cats (n = 6) were randomly allocated to receive T (3 mg/kg) intravenously (IV), T (5 mg/kg) orally (PO), or T (5 mg/kg) and G (10 mg/kg) PO with a 1-week washout period between treatments. Heart rate, respiratory rate, indirect blood pressure, and level of sedation were assessed, and venous blood samples were collected serially over 24 h. Analysis of plasma trazodone concentration was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral T administration resulted in a bioavailability of 54.9(7-96)%, and 17.2(11-25)% when administered with G. T_max 0.17 (0.17-0.5) and 0.17 (0.17-0.75) h; C_max 1.67 ± 0.91 and 1.22 ± 0.54 μg/mL, AUC 5.23 (2.0-18.76) and 2.37 (1.17-7.80) h*μg/mL; T_1/2 5.12 ± 2.56 and 4.71 ± 1.07 h; for T and TG, respectively. Sedation was significant when compared to baseline in all groups from 20 or 45 min to 8 h indicating some lag between peak plasma concentration and sedative effects. Physiological variables remained within normal limits. This study concludes that oral trazodone is rapidly absorbed in healthy cats. Addition of gabapentin did not result in more profound sedation, showing no clinical advantage of combining these drugs in this study population.

Keywords: cats; gabapentin; oral sedatives; pharmacokinetics; trazodone.