To determine the pharmacokinetics and pharmacodynamics of methadone after IV or IM administration to isoflurane-anesthetized chickens.
6 healthy adult Hy-Line hens.
In a randomized crossover-design study, methadone (6 mg/kg) was administered IV and IM to isoflurane-anesthetized chickens with a 1-week washout period between experiments. Blood samples were collected immediately before and at predetermined time points up to 480 minutes after methadone administration. Plasma concentrations were determined by liquid chromatography–mass spectrometry, and appropriate compartmental models were fit to the plasma concentration-versus-time data. Cardiorespiratory variables were compared between treatments and over time with mixed-effect repeated-measures analysis.
A 3-compartment model best described the changes in plasma methadone concentration after IV or IM administration. Estimated typical values for volumes of distribution were 692 mL/kg for the central compartment and 2,439 and 2,293 mL/kg for the first and second peripheral compartments, respectively, with metabolic clearance of 23.3 mL/kg/min and first and second distributional clearances of 556.4 and 51.8 mL/kg/min, respectively. Typical bioavailability after IM administration was 79%. Elimination half-life was 177 minutes, and maximum plasma concentration after IM administration was 950 ng/mL. Heart rate was mildly decreased at most time points beginning 5 minutes after IV or IM drug administration.
CONCLUSIONS AND CLINICAL RELEVANCE
Disposition of methadone in isoflurane-anesthetized chickens was characterized by a large volume of distribution and moderate clearance, with high bioavailability after IM administration. Additional studies are warranted to assess pharmacokinetics and pharmacodynamics of methadone in awake chickens.
Objective—To determine hepatotoxicity of stanozolol
in cats and to identify clinicopathologic and
histopathologic abnormalities in cats with stanozololinduced
Design—Clinical trial and case series.
Animals—12 healthy cats, 6 cats with chronic renal
failure, and 3 cats with gingivitis and stomatitis.
Procedures—Healthy cats and cats with renal failure
were treated with stanozolol (25 mg, IM, on the first
day, then 2 mg, PO, q 12 h) for 4 weeks. Cats with
gingivitis were treated with stanozolol at a dosage of
1 mg, PO, every 24 hours.
Results—Most healthy cats and cats with renal failure
developed marked inappetence, groomed less,
and were less active within 7 to 10 days after initiation
of stanozolol administration. Serum alanine transaminase
(ALT) activity was significantly increased in 14 of
18 cats after stanozolol administration, but serum
alkaline phosphatase activity was mildly increased in
only 3. Four cats with serum ALT activity > 1,000 U/L
after only 2 weeks of stanozolol administration had
coagulopathies; administration of vitamin K resolved
the coagulopathy in 3 of the 4 within 48 hours. All 18
cats survived, and hepatic enzyme activities were
normal in all cats tested more than 4 weeks after
stanozolol administration was discontinued. Two of
the 3 cats with gingivitis developed evidence of
severe hepatic failure 2 to 3 months after initiation of
stanozolol treatment; both cats developed coagulopathies.
Histologic evaluation of hepatic biopsy
specimens from 5 cats revealed diffuse hepatic lipidosis
and cholestasis without evidence of hepatocellular
Conclusions and Clinical Relevance—Results suggest
that stanozolol is hepatotoxic in cats. (J Am Vet
Med Assoc 2000;217:681–684)