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Correction of fasting hyperglycaemia with insulin or sulphonylurea lowers fasting ketone levels, but does not alter resting or post-glucose energy expenditure in non insulin dependent diabetes. Differences between the OGTT and the glucose clamp.

Sixteen non-obese non insulin dependent diabetic patients had a 75 g oral glucose tolerance test with simultaneous measurement of intermediary metabolites and of overall energy expenditure by indirect calorimetry during the test. The same patients had a 3H3 glucose infusion and hyperinsulinaemic glucose clamp procedure with glucose held at 10.0 mmol/l and insulin infused at 40 mU/m2/min. The changes in glucose and fat metabolism, in total energy balance and the fall in RQ during the glucose tolerance test did not correlate with the measures of hepatic glucose output or peripheral insulin resistance in these patients. Although the concept of insulin resistance is useful in considering the non insulin dependent diabetic state, the data derived from the body responses to a single glucose load are more relevant to the day to day fluctuation of the internal environment.

Blood Glucose↗

The pharmacokinetics of phenobarbitone in fasting and non-fasting dogs.

The pharmacokinetics of oral phenobarbitone was studied in 10 clinically healthy adult dogs. The drug was given once daily in tablet form, at a dose of 5 mg kg-1 of body mass. Serial venous blood samples (n = 9) were collected from each dog on Day 1 (the first day of drug dosing), on Day 22, and on Day 24 after continuous dosing. Trough serum concentrations were determined on Day 7, Day 14 and Day 21. The drug was administered to the dogs on an empty stomach, except on Day 24, when it was given with food, in order to assess the influence of food on its absorption. Drug serum concentrations were described by a one-compartmental open model with first order absorption and elimination. An average steady-state trough serum level of phenobarbitone of 52,96 +/- 8.40 mmol l-1 was achieved after 3 weeks of daily dosing. The mean elimination half-lives for Day 1 and Day 22 were 46.3 +/- 11.3 h and 29.3 +/- 4.6 h respectively. The area under the curve for Day 22 was 1,656.17 +/- 186.45 mumol h-1 l-1 and for Day 24 was 1,493.06 +/- 205.4 mumol h-1 l-1. The mean clearance value for Day 22 was 0.0133 +/- 0.0016 l h-1 kg-1. Side effects of polyphagia, polydipsia, sedation and ataxia were commonly observed in the first 2-9 d, but disappeared thereafter. It was concluded that a dose of 5 mg kg-1 would achieve an average serum concentration of 64.59 mumol l-1 in adult dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗