Pharmacokinetics of a high-concentration formulation of buprenorphine (Simbadol) in male dogs.

OBJECTIVE: To describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: A total of six healthy male intact Beagle dogs, aged 9-13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation). METHODS: Dogs were randomized to be administered buprenorphine (0.12 mg kg-1; Simbadol, 1.8 mg mL-1) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography-tandem mass spectrometry. RESULTS: A three-compartment model with zero or biphasic rapid and slow first-order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first-order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg-1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute-1 kg-1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80-239)%. Calculated terminal half-life was 963 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: The high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues.

Orthostatic hypotension secondary to a suspected thymoma in a dog: a case report.

BACKGROUND: This is the first case report description, to our knowledge, of a cranial mediastinal mass (suspected thymoma) causing orthostatic hypotension in a dog. CASE PRESENTATION: A Labrador Retriever presented for urethral stent placement during cystoscopy secondary to transitional cell carcinoma diagnosis. During anesthesia, the patient had unexpected severe and poorly-responsive hypotension following a shift in position. Several days later, an intrathoracic mass was discovered, raising concerns that the position of the mass in relation to the great vessels and heart may have been the cause of the hypotension. The patient returned for a second stent placement, and computed tomography of the chest confirmed a cranial mediastinal mass, most suspected to be thymoma based on the results of cytology. The patient was kept in sternal recumbency, but when re-positioning to left lateral recumbency, there was a dramatic blood pressure drop that corrected with a return to sternal positioning. CONCLUSIONS: To our knowledge, orthostatic hypotension has not been described in relation to thymoma in dogs. Thymomas are rare; however, they may be associated with disease of autonomic dysfunction, such as myasthenia gravis, that may lead to orthostatic hypotension. This has been described within the human literature, and we hypothesize it was present in the currently described case. Concurrently, thymomas may grow to a substantial size and cause direct compression of the intrathoracic vasculature. As such, it should be on the differential list for poorly-responsive hypotension following a shift in body positioning under anesthesia.