Hepatic clearance and biliary excretion of model substrates for each of four carrier-mediated transport systems were studied in male Sprague-Dawley rats treated 28 days earlier with 45 mg/kg streptozotocin iv to induce uncontrolled insulin-deficient diabetes. Diabetic rats exhibited hyperglycemia (560 mg/dl), polyuria (160 ml/24 hr), polyphagia, polydipsia, and generalized myopathy. The plasma disappearance, biliary excretion, and elimination half-life of the anionic dye phenol red was unchanged in diabetic rats, but total clearance of phenol red was increased. Conjugation of phenol red with glucuronic acid appeared to be increased in diabetic rats, whereas acetylation of procainamide ethobromide was decreased. Plasma elimination and total clearance of cationic procainamide ethobromide, uncharged ouabain, and the bile acid taurocholate were significantly increased in diabetic animals. Biliary excretion of these three compounds was only slightly elevated in the first 15 min after administration and was decreased after 1 hr. Biliary and total systemic clearance were also increased from 2-3-fold for procainamide ethobromide, ouabain, and taurocholate. These changes in clearance are predominantly due to the 2-5-fold increase in steady state volume of distribution. Basal bile flow rates were increased by 62% after the induction of diabetes to 88 μl/min/kg. Diabetic rats secreted higher levels of bile acids, cholesterol, and phospholipids into bile. These data indicate that long term insulin-dependent diabetes does alter hepatic excretory function.
|Original language||English (US)|
|Number of pages||7|
|Journal||Drug Metabolism and Disposition|
|State||Published - Jan 1 1987|
ASJC Scopus subject areas
- Pharmaceutical Science