GASTRIC-EMPTYING IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUSAND BIOAVAILABILITY OF THIOCTIC ACID-ENANTIOMERS

The objective of this study was to determine the impact of prolonged g astric emptying in patients with insulin dependent diabetes mellitus ( IDDM) on the bioavailability of the R(+)- and S(-)-thioctic acid (TA) enantiomers. Gastric emptying time (GET) was assessed in 30 healthy vo lunteers and 22 patients with IDDM using sequential ultrasonography af ter a standardized solid-liquid test meal. Pharmacokinetics and absolu te bioavailability (F) of the TA-enantiomers were studied using a rand omized, open two-way crossover design with administrations of oral and intravenous single doses of 200 mg rac-TA. GET in healthy subjects wa s 134.7+/-21.6 min, the normal range was calculated from 88.3 to 181.1 min. The mean GET in all IDDM patients was significantly prolonged (1 78.2+/-28.1 min; P < 0.001). Only 50% of the patients (n=11) were foun d to have normal GET (group A), the other half of the population (n=11 ) were considered to have delayed GET (group B). Mean GET values were 156.9+/-21.5 in group A (P=0.028) and 199.4+/-13.9 min in group B, res pectively, suggesting that gastric motility is significantly different from non-diabetic controls even in patients with apparently normal ga stric emptying. Times to peak plasma concentrations (t(max)) of both T A-enantiomers were similar in both groups and thus, unrelated to measu res of gastric emptying. In contrast, maximum concentrations (C-max) a nd area-under-the-curve values (AUC) of both enantiomers were reduced by about 30% in patients with delayed GET. Although these differences resulted in statistical significance for the AUC of both enantiomers ( P<0.05), linear regression analysis showed only modest correlation bet ween GET and the extent of TA-enantiomer absorption (r(2) = 0.31 and 0 .22 for R(+)-/S(-)-TA, respectively). The study suggests that prolonge d gastric emptying is frequently present in IDDM. Delayed gastric empt ying, however, does not substantially affect the rare and extent of ab sorption of both TA-enantiomers. (C) 1997 Elsevier Science B.V.