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- Author or Editor: Renata L. Linardi x
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Abstract
Objective—To evaluate the effects of epidural administration of hydromorphone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses.
Animals—6 healthy adult horses.
Procedure—Horses were assigned to receive hydromorphone (0.04 mg/kg) or a control solution (20 mL of sterile water) administered epidurally into in the first intercoccygeal space. Treatments were administered at time intervals of ≥ 7 days. Electrical stimulation was applied for 6 hours after epidural injection over the dermatomes of the perineal, sacral, lumbar, and thoracic regions, and the avoidance threshold voltage was recorded.
Results—Administration of sterile water did not change the avoidance threshold. Hydromorphone significantly increased the avoidance threshold by 20 minutes after injection, which lasted until 250 minutes after epidural administration in the perineal, sacral, lumbar, and thoracic regions. Profound analgesia (avoidance threshold > 40 V) was achieved only in the perineal region at 60 minutes after epidural administration of hydromorphone. Analgesia for all dermatomes was considered moderate for 250 minutes after epidural injection.
Conclusions and Clinical Relevance—Epidural administration of hydromorphone increases the avoidance threshold to noxious electrical stimulation in the perineal, lumbar, sacral, and thoracic regions in horses for 250 minutes after injection. Hydromorphone epidural administration may prove useful in the management of horses with pain of moderate to mild intensity.
Abstract
Objective—To evaluate the effects of subarachnoidally administered hyperbaric morphine, buprenorphine, and methadone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses.
Animals—6 healthy adult horses.
Procedures—Horses were assigned to receive subarachnoid administration of hyperbaric morphine (0.01 mg/kg), buprenorphine (0.001 mg/kg), methadone (0.01mg/kg), or 10% dextrose solution in equal volumes (5 mL). Electrical stimulation was applied every 10 minutes for 60 minutes and every 30 minutes for 120 minutes after subarachnoid injection over the dermatomes of the perineal, sacral, lumbar, and thoracic regions, and the avoidance threshold voltage was recorded. Heart and respiratory rate, blood gas tensions, serum electrolyte concentrations, and sedative effects were also evaluated.
Results—Administration of 10% dextrose solution did not change the avoidance threshold. Morphine and methadone significantly increased the avoidance threshold by 10 minutes after injection, which lasted until 120 minutes after subarachnoid administration in the perineal, sacral, lumbar, and thoracic regions. Profound analgesia (avoidance threshold > 40 V) was achieved in all regions. Buprenorphine also significantly increased the avoidance threshold by 10 minutes (36 V) after injection, which lasted 60 minutes and was considered moderate. Heart rate, blood pressure, respiratory rate, and blood gas tensions stayed within reference range. No ataxia, signs of sedation, or CNS excitement were observed.
Conclusions and Clinical Relevance—Subarachnoid administration of hyperbaric morphine or methadone produces intense analgesia for 120 minutes over the dermatomes of the perineal, sacral, lumbar, and thoracic areas without cardiorespiratory depression, ataxia, or CNS excitement in horses.
Abstract
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.
