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Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80°C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species.

The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values ofor =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICsor =0.5 microg/ml, more frequent dosing or a higher dosage may be required.

Aspergillus spp. fungal infections are the most common cause of morbidity and mortality in captive penguins. Itraconazole has been the drug of choice for both therapeutic and prophylactic treatment; however, the pharmacokinetic and pharmacodynamic parameters can be highly variable in different species, and it has not been evaluated in penguins. In this study, four preliminary steady-state trials were performed to compare two oral formulations of itraconazole (commercial capsules compared with generic bulk compounded powder) at two different dosages (6 or 12 mg/kg once a day) administered in fish to small groups of captive Humboldt penguins (Spheniscus humboldti). Building on this data, a final steady-state trial was performed with the use of a 7 mg/kg oral dosage twice a day of commercial capsules given in fish to a group of 15 penguins. With sparse sampling, blood was drawn for testing from small subsets of each treatment group at 4-7 time points in the 24-hr period after the final dose of itraconazole on day 14. Steady-state plasma concentrations of itraconazole and hydroxyitraconazole, the major metabolite, were determined by reverse phase high-performance liquid chromatography with fluorescence detection. Treatment with the generic bulk compounded product resulted in plasma levels of itraconazole that were undetectable for 26 out of 30 blood samples, compared with seven out of 20 blood samples for the commercial product at the same dosage. On the basis of study results, an estimated oral dosage of either 8.5 mg/kg twice a day or 20 mg/kg once a day of the commercial itraconazole capsules given in fish would produce adequate steady-state therapeutic blood levels in Humboldt penguins.