Pharmacokinetic comparison of two buprenorphine formulations after buccal administration in healthy male cats

• Published in: Journal of feline medicine and surgery 2018-04, Vol.20 (4), p.312-318
• Main Authors: Gulledge, Brett M, Messenger, Kristen M, Cornell, Karen K, Lindell, Heather, Schmiedt, Chad W
• Format: Article
• Language: English
• Subjects: Administration, Buccal; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacokinetics; Animals; Area Under Curve; Buprenorphine - administration & dosage; Buprenorphine - pharmacokinetics; Cats; Cross-Over Studies; Half-Life; Male; Original; Pain - drug therapy; Pain - veterinary; Pain Measurement - veterinary; Random Allocation
• ISSN: 1098-612X; 1532-2750
• DOI: 10.1177/1098612X17710843

Objectives The objective of this study was to compare the pharmacokinetics of compounded and commercially available aqueous formulations of buprenorphine after a single buccal dose to healthy cats and to evaluate the concentrations of a compounded buprenorphine solution over 21 days when stored at room temperature (RT; 22–24°C) with exposure to light or when refrigerated at 4°C while protected from light. Methods Six young healthy male cats were administered single buccal doses of compounded and commercially available formulations of buprenorphine (0.03 mg/kg) using a randomized, blinded, two-period crossover design. Blood samples were obtained over a 24 h period and plasma buprenorphine concentrations were determined using ultra-high-pressure liquid chromatography with mass spectrometry detection. Three batches of the compounded formulation were stored at RT or 4°C and aliquots were evaluated over 21 days for buprenorphine concentration using high-performance liquid chromatography with fluorescence detection. Results Plasma concentrations of buprenorphine were above the limit of quantification up to 6 h in some cats and up to 3 h in all cats. The area under the curve was significantly less for the compounded formulation (P = 0.004). A significant difference was not detected between formulations for time to maximum concentration (P = 0.11), maximum concentration (P = 0.06), half-life (P = 0.88) and mean residence time (P = 0.57). Buprenorphine concentration in the compounded formulation was not affected by storage condition or time and remained between 90% and 110% of the target concentration at all time points. Conclusions and relevance A buprenorphine solution prepared from sublingual tablets is absorbed after buccal administration in healthy cats. The extent of absorption is significantly less than that of the commercially available formulation. The compounded solution maintains an acceptable buprenorphine concentration for at least 21 days when stored at RT or refrigerated.