Case Description—3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product.
Clinical Findings—All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry.
Treatment and Outcome—Propranolol (0.01 mg/kg [0.005 mg/lb], IV) was administered to all 3 horses for antagonism of β-adrenergic effects and caused a transient decrease in heart rate in all patients. All horses also received crystalloid fluids IV and other supportive treatment measures. Two horses were euthanatized (2 and 4 days after admission) because of complications. One horse recovered and was discharged 4 days after admission to the hospital. In the 2 nonsurviving horses, skeletal and cardiac muscle necrosis was evident at necropsy, and tissue clenbuterol concentrations were highest in the liver.
Clinical Relevance—Clenbuterol is a β2-adrenergic receptor agonist licensed for veterinary use as a bronchodilator. At doses ≥ 10 2μg/kg (4.5 μg/lb), in excess of those normally prescribed, β-adrenergic stimulation by clenbuterol may cause sustained tachycardia, muscle tremors, hyperglycemia, and cardiac and skeletal muscle necrosis. Laminitis, acute renal failure, rhabdomyolysis, and cardiomyopathy were fatal complications associated with clenbuterol overdose in 2 horses in the present report. At the dose administered, propranolol was effective for short-term control of sinus tachycardia, but it did not alleviate all clinical signs in patients in the present report. These cases demonstrated the risks associated with the use of nonprescribed compounded medications for which the ingredients may be unknown.
Objective—To determine the effects of clenbuterol, at a dosage of up to 3.2 μg/kg for 14 days, PO, on skeletal and cardiac muscle in healthy horses undergoing treadmill exercise.
Animals—12 healthy horses from 3 to 10 years old.
Procedures—Horses were randomly assigned to a control group (n = 6) or clenbuterol group (6) and received either saline (0.9% NaCl) solution or clenbuterol, PO, every 12 hours for 14 days. Horses were subjected to submaximal treadmill exercise daily during treatment. Muscle biopsy specimens were collected before and after treatment for determination of apoptosis. Echocardiographic measurements, serum clenbuterol and cardiac troponin I concentrations, and serum activities of creatine kinase and aspartate aminotransferase were measured before, during, and after treatment. Jugular venous blood samples were collected every 3 days during treatment. Echocardiography was repeated every 7 days after beginning treatment. Response variables were compared between treatment groups and across time periods.
Results—No significant effect of clenbuterol or exercise on response variables was found between treatment and control groups at any time point or within groups over time.
Conclusions and Clinical Relevance—Results did not reveal any adverse effects of treatment with an approved dose of clenbuterol on equine cardiac or skeletal muscle in the small number of horses tested.
Objective—To determine the plasma pharmacokinetics
of imipenem (5 mg/kg) after single-dose IV, IM,
and SC administrations in dogs and assess the ability
of plasma samples to inhibit the growth of Escherichia
coli in vitro.
Animals—6 adult dogs.
Procedure—A 3-way crossover design was used.
Plasma concentrations of imipenem were measured
after IV, IM, and SC administration by use of high-performance
liquid chromatography. An agar well antimicrobial
assay was performed with 3 E coli isolates
that included a reference strain and 2 multidrug-resistant
Results—Plasma concentrations of imipenem
remained above the reported minimum inhibitory concentration
for E coli (0.06 to 0.25 µg/mL) for a minimum
of 4 hours after IV, IM, and SC injections.
Harmonic mean and pseudo-standard deviation halflife
of imipenem was 0.80 ± 0.23, 0.92 ± 0.33, and
1.54 ± 1.02 hours after IV, IM, and SC administration,
respectively. Maximum plasma concentrations (Cmax)
of imipenem after IM and SC administration were
13.2 ± 4.06 and 8.8 ± 1.7 mg/L, respectively. Time
elapsed from drug administration until Cmax was 0.50
± 0.16 hours after IM and 0.83 ± 0.13 hours after SC
injection. Growth of all 3 E coli isolates was inhibited
in the agar well antimicrobial assay for 2 hours after
imipenem administration by all routes.
Conclusions and Clinical Relevance—Imipenem is
rapidly and completely absorbed from intramuscular
and subcutaneous tissues and effectively inhibits in
vitro growth of certain multidrug-resistant clinical isolates
of E coli. (Am J Vet Res 2003;64:694–699)
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.
Objective—To evaluate the pharmacokinetics of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis).
Animals—9 healthy adult Hispaniolan Amazon parrots of unknown sex.
Procedures—Nalbuphine decanoate (37.5 mg/kg) was administered IM to all birds. Plasma samples were obtained from blood collected before (time 0) and 0.25, 1, 2, 3, 6, 12, 24, 48, and 96 hours after drug administration. Plasma samples were used for measurement of nalbuphine concentrations via liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were estimated with computer software.
Results—Plasma concentrations of nalbuphine increased rapidly after IM administration, with a mean concentration of 46.1 ng/mL at 0.25 hours after administration. Plasma concentrations of nalbuphine remained > 20 ng/mL for at least 24 hours in all birds. The maximum plasma concentration was 109.4 ng/mL at 2.15 hours. The mean terminal half-life was 20.4 hours.
Conclusions and Clinical Relevance—In Hispaniolan Amazon parrots, plasma concentrations of nalbuphine were prolonged after IM administration of nalbuphine decanoate, compared with previously reported results after administration of nalbuphine hydrochloride. Plasma concentrations that could be associated with antinociception were maintained for 24 hours after IM administration of 37.5 mg of nalbuphine decanoate/kg. Safety and analgesic efficacy of nalbuphine treatments in this species require further investigation to determine the potential for clinical use in pain management in psittacine species.
Objective—To compare plasma endothelin (ET)- like
immunoreactivity between healthy horses and those
with naturally acquired gastrointestinal tract disorders.
Animals—29 healthy horses and 142 horses with
gastrointestinal tract disorders.
Procedure—Blood samples were collected from
healthy horses and from horses with gastrointestinal
tract disorders prior to treatment. Magnitude and
duration of abnormal clinical signs were recorded, and
clinical variables were assessed via thorough physical
examinations. Plasma concentrations of ET-like
immunoreactivity were measured by use of a radioimmunoassay
for human endothelin-1, and CBC and
plasma biochemical analyses were performed.
Results—Plasma ET-like immunoreactivity concentration
was significantly increased in horses with gastrointestinal
tract disorders, compared with healthy
horses. Median plasma concentration of ET-like
immunoreactivity was 1.80 pg/ml (range, 1.09 to 3.2
pg/ml) in healthy horses. Plasma ET-like immunoreactivity
was greatest in horses with strangulating largeintestinal
obstruction (median, 10.02 pg/ml; range, 3.8
to 22.62 pg/ml), peritonitis (9.19 pg/ml; 7.89 to 25.83
pg/ml), and enterocolitis (8.89 pg/ml; 6.30 to 18.36
pg/ml). Concentration of ET-like immunoreactivity was
significantly associated with survival, PCV, and duration
of signs of pain. However, correlations for associations
with PCV and duration of pain were low.
Conclusions and Clinical Relevance—Horses with
gastrointestinal tract disorders have increased plasma
concentrations of ET-like immunoreactivity, compared
with healthy horses. The greatest values were detected
in horses with large-intestinal strangulating
obstructions, peritonitis, and enterocolitis. This suggests
a potential involvement of ET in the pathogenesis
of certain gastrointestinal tract disorders in horses.
(Am J Vet Res 2002;63:454–458)
Objective—To assess the pharmacokinetics of nalbuphine HCl after IV and IM administration to Hispaniolan Amazon parrots (Amazona ventralis).
Animals—8 healthy adult Hispaniolan Amazon parrots of unknown sex.
Procedures—Nalbuphine HCl (12.5 mg/kg) was administered IV and IM to all birds in a complete randomized crossover study design; there was a washout period of 21 days between subsequent administrations. Plasma samples were obtained from blood collected at predetermined time points for measurement of nalbuphine concentration by use of liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were estimated by use of computer software.
Results—Nalbuphine was rapidly eliminated with a terminal half-life of 0.33 hours and clearance of 69.95 mL/min/kg after IV administration and a half-life of 0.35 hours after IM administration. Volume of distribution was 2.01 L/kg after IV administration. The fraction of the dose absorbed was high (1.03) after IM administration. No adverse effects were detected in the parrots during the study.
Conclusions and Clinical Relevance—In Hispaniolan Amazon parrots, nalbuphine appeared to have good bioavailability after IM administration and was rapidly cleared after IV and IM administration. Safety and analgesic efficacy of various nalbuphine treatment regimens in this species require further investigation to determine the potential for clinical palliation of signs of pain in psittacine species.
CASE DESCRIPTION An adult sexually intact female Harris hawk (Parabuteo unicinctus) housed at a wildlife hospital was evaluated because of acute collapse during an educational exhibition.
CLINICAL FINDINGS Physical examination and hematologic analysis revealed no abnormalities; radiography revealed findings consistent with a previous tibiotarsal fracture. Coelioscopy with histologic examination and fungal culture of lung and air sac samples revealed anthracosis but no fungal infection. The hawk was discharged and temporarily removed from the education program; 1 month later, upon reintroduction into the program, it collapsed again. Physical examination and hematologic findings were similar to those after the first episode. Transcoelomic and transesophageal echocardiography and CT angiocardiography findings were consistent with cardiomyopathy.
TREATMENT AND OUTCOME Initial cardiac treatment included furosemide (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) and pimobendan (10 mg/kg [4.5 mg/lb], PO, q 12 h). After 10 days of treatment, peak and trough plasma concentrations of pimobendan were measured at 25, 196 and 715.97 ng/mL, respectively; the dosage was decreased to 0.25 mg/kg (0.11 mg/lb), PO, every 12 hours. No overt signs of toxicosis were detected. A sample was collected to reevaluate plasma pimobendan concentration after 30 days of treatment; results were not obtained prior to the patient's death but revealed a peak concentration of 16.8 ng/mL, with an undetectable trough concentration. The hawk was found dead 6 months after initial evaluation. Necropsy revealed cardiomegaly, but histologic examination did not reveal an inciting cause of cardiac dysfunction.
CLINICAL RELEVANCE Cardiac disease in raptors may be underreported. Transcoelomic and transesophageal echocardiography and CT angiography provided useful information for the diagnosis of cardiac disease in the hawk of this report.