Objective—To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses.
Animals—6 healthy adult horses.
Procedures—Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography–mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects.
Results—In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration.
Conclusions and Clinical Relevance—Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.
Sodium salicylate was administered to cattle and goats iv and po according to a crossover design. Total urinary excretion of sa and its metabolites was measured for 3 days after dosing. Salicyluric acid (sua) was the only metabolite detected in urine of either species. Recovery of sodium salicylate and sua in goats amounted to 67.9 and 34.6% of the dose, respectively, after iv administration. After oral dosing, total recoveries were 30.2% (sodium salicylate) and 71.7%(sua) of dose. By comparison, cattle excreted significantly (P < 0.05) less sodium salicylate (54.0%) and more sua (49.9%) after iv dosing. The same pattern was observed after oral administration, wherein cattle excreted < 12% as sodium salicylate and more than 99% as sua. In both species, almost 90% of the drug excreted as sodium salicylate was found in urine within the first 12 hours after an iv dose and within 24 hours after oral dosing. The excretion of sua was somewhat slower in both species, especially after oral administration. The data suggested that there were only quantitative differences in the metabolism and elimination of sodium salicylate between the 2 species, with cattle excreting a higher proportion of the drug as the glycine conjugate sua.