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September • 2008
 
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Acid-base and hormonal abnormalities in dogs with naturally occurring diabetes mellitus
 

This cross-sectional study of 48 diabetic dogs examined and compared their acid-base and hormonal abnormalities with those of 17 healthy dogs.

Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups.

Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 µmol/L had a serum insulin concentration < 5 µU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum ß-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased.

Conclusions and Clinical Relevance Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

Reference: Durocher et al. JAVMA 232: 1310-1320, 2008.

 
Effects of ketoconazole on the pharmacokinetics and pharmacodynamics of morphine in healthy greyhounds
 

Healthy greyhounds (3 male, 3 female) were studied to assess pharmacokinetics and pharmacodynamics of morphine and the effects of ketoconazole on these parameters.

Morphine sulfate (0.5 mg/kg. IV) was administered to greyhounds prior to and after 5 days of ketoconazole (12.7 ± 0.6 mg/kg, PO) treatment. Plasma samples were obtained from blood samples collected at predetermined time points for measurement of morphine and ketoconazole concentrations by mass spectrometry. Pharmacokinetics of morphine were estimated by use of computer software.

Pharmacodynamic effects of morphine in greyhounds were similar to those of other studies in dogs and were similar between treatment groups. Morphine was rapidly eliminated with a half-life of 1.28 hours and a plasma clearance of 32.55 mL/min/kg. The volume of distribution was 3.6 L/kg. No significant differences in the pharmacokinetics of morphine were found after treatment with ketoconazole. However, plasma concentrations of ketoconazole were high and persisted longer than expected in greyhounds.

Conclusions and Clinical Relevance Ketoconazole had no significant effect on morphine pharmacokinetics, and the pharmacodynamics were similar between treatment groups. Plasma concentrations of ketoconazole were higher than expected and persisted longer than expected in greyhounds.

Reference: Kukanich and Borum. AJVR 69:664–669; 2008.

 
 
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