Zysset T, Wietholtz H
Department of Clinical Pharmacology University of Berne, Switzerland.
Eur J Clin Pharmacol. 1988;34(4):369-75. doi: 10.1007/BF00542438.
As the influence of diabetes on drug metabolism in patients is controversial, a study was performed to assess antipyrine (AP) disposition in controlled Type I and Type II diabetics and 2 age- and sex-matched control groups. In Type I diabetics, the half-life of AP was significantly reduced from 12.0 (controls) to 7.9 h, and the volume of distribution (V) was lowered from 733 to 569 ml.kg-1. The resulting plasma clearance and cumulative urinary excretion of AP and its metabolites over 24 h did not differ from controls. In Type II diabetics, the AP half-life (14.5 h) and V (568 ml.kg-1) did not differ from their age- and sex-matched controls (11.1 h and 643 ml.kg-1, respectively), but the plasma clearance of AP was significantly reduced by 30%, and urinary excretion was significantly reduced to 44% of controls. The differential effects of Types I and II diabetes on AP metabolism may explain, at least in part, the controversial data in the literature.
由于糖尿病对患者药物代谢的影响存在争议,因此开展了一项研究,以评估在控制良好的Ⅰ型和Ⅱ型糖尿病患者以及两个年龄和性别匹配的对照组中安替比林(AP)的处置情况。在Ⅰ型糖尿病患者中,AP的半衰期从12.0小时(对照组)显著缩短至7.9小时,分布容积(V)从733降至569 ml.kg-1。24小时内AP及其代谢产物的血浆清除率和累积尿排泄量与对照组无差异。在Ⅱ型糖尿病患者中,AP半衰期(14.5小时)和V(568 ml.kg-1)与年龄和性别匹配的对照组(分别为11.1小时和643 ml.kg-1)无差异,但AP的血浆清除率显著降低30%,尿排泄量显著降至对照组的44%。Ⅰ型和Ⅱ型糖尿病对AP代谢的不同影响可能至少部分解释了文献中存在争议的数据。