Gastric emptying in patients with insulin dependent diabetes mellitus and bioavailability of thioctic acid-enantiomers

被引:15
作者
Hermann, R
Wildgrube, HJ
Ruus, P
Niebch, G
Nowak, H
Gleiter, CH
机构
[1] ASTA Med AG, Med Res, Dept Clin Pharmacol, D-60314 Frankfurt, Germany
[2] Inst Appl Diagnost, Hanau, Germany
[3] ASTA Med AG, Corp Res, Dept Biochem, D-60314 Frankfurt, Germany
[4] ASTA Med AG, Corp Res, Dept Biometr, D-60314 Frankfurt, Germany
[5] Univ Gottingen, Dept Clin Pharmacol, D-3400 Gottingen, Germany
关键词
thioctic acid; alpha-lipoic acid; autonomic neuropathy; bioavailability; diabetic neuropathy; gastric emptying;
D O I
10.1016/S0928-0987(97)00065-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of this study was to determine the impact of prolonged gastric 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 volunteers and 22 patients with IDDM using sequential ultrasonography after a standardized solid-liquid test meal. Pharmacokinetics and absolute bioavailability (F) of the TA-enantiomers were studied using a randomized, open two-way crossover design with administrations of oral and intravenous single doses of 200 mg rac-TA. GET in healthy subjects was 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 (178.2+/-28.1 min; P < 0.001). Only 50% of the patients (n=11) were found 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, respectively, suggesting that gastric motility is significantly different from non-diabetic controls even in patients with apparently normal gastric emptying. Times to peak plasma concentrations (t(max)) of both TA-enantiomers were similar in both groups and thus, unrelated to measures of gastric emptying. In contrast, maximum concentrations (C-max) and 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 between GET and the extent of TA-enantiomer absorption (r(2) = 0.31 and 0.22 for R(+)-/S(-)-TA, respectively). The study suggests that prolonged gastric emptying is frequently present in IDDM. Delayed gastric emptying, however, does not substantially affect the rare and extent of absorption of both TA-enantiomers. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:27 / 37
页数:11
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