Kudo T, Toda T, Ushiki T, Ohi K, Ikarashi N, Ochiai W, Sugiyama K
Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, Japan.
Xenobiotica. 2010 Apr;40(4):282-90. doi: 10.3109/00498251003596809.
The pharmacokinetics of drugs can change in diabetes mellitus and even among diabetics. They may differ between type I diabetes (T1DM) and type 2 diabetes (T2DM). As triazolam was administered orally to Tsumura, Suzuki, obese, diabetes (TSOD) mice and streptozotocin (STZ) mice, clearance per body (CL/F) in TSOD mice did not differ compared with Tsumura, Suzuki, non-obesity (TSNO) mice. In STZ mice, CL/F was greater than in control mice. Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice. No significant difference existed in small intestinal Cyp3a expression between STZ mice and control mice. In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice. These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations. This may be a factor in the difference in the drug pharmacokinetics between T2DM and T1DM patients.
药物的药代动力学在糖尿病患者中会发生变化，甚至在糖尿病患者之间也存在差异。它们在1型糖尿病（T1DM）和2型糖尿病（T2DM）之间可能有所不同。由于对津村、铃木、肥胖、糖尿病（TSOD）小鼠和链脲佐菌素（STZ）小鼠口服了三唑仑，TSOD小鼠的每单位体重清除率（CL/F）与津村、铃木、非肥胖（TSNO）小鼠相比没有差异。在STZ小鼠中，CL/F高于对照小鼠。TSOD小鼠小肠细胞色素P450（Cyp）3a表达明显低于TSNO小鼠。STZ小鼠和对照小鼠之间小肠Cyp3a表达没有显著差异。在胰岛素治疗的小鼠中，小肠Cyp3a表达明显低于对照小鼠。这些结果表明，T1DM和T2DM之间小肠Cyp3a表达变化的差异可能是由于血浆胰岛素浓度的差异。这可能是T2DM和T1DM患者药物药代动力学差异的一个因素。
