Charland S L, Bartlett D L, Torosian M H
Department of Pharmacy Practice and Administration, Philadelphia College of Pharmacy and Science, Pennsylvania, USA.
Nutrition. 1995 Mar-Apr;11(2):154-8.
Previous studies indicate that glutamine-supplemented diets decrease the enterocolitis associated with methotrexate administration. The influence of glutamine on the pharmacokinetics of methotrexate and the formation of its major hepatic metabolite, 7-hydroxy-methotrexate was examined in 36 adult, female Lewis rats. Animals were randomly assigned to receive either a 3% glycine-supplemented solid diet (GLY; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) or a 3% glutamine-supplemented solid diet (GLN; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) ad libitum for 35 days. Animals were separated into two groups (serum methotrexate pharmacokinetics, n = 20; or methotrexate renal elimination, n = 16) and given a 10 mg/kg dose of methotrexate. There was a 25% decrease in mean methotrexate total serum clearance in the GLN group compared with the control group (0.63 +/- 0.09 L.h-1.kg-1 and 0.47 +/- 0.13 L.h-1.kg-1, respectively, p = 0.01). Renal methotrexate elimination was decreased by 65%. There was no significant difference in methotrexate volume of distribution or half-life between the two groups. Glutamine decreases methotrexate systemic clearance, thus exposing the host as well as the tumor to greater methotrexate concentrations.
先前的研究表明，补充谷氨酰胺的饮食可降低与甲氨蝶呤给药相关的小肠结肠炎。在36只成年雌性Lewis大鼠中，研究了谷氨酰胺对甲氨蝶呤药代动力学及其主要肝代谢产物7-羟基甲氨蝶呤形成的影响。动物被随机分配自由采食3%甘氨酸补充的固体饮食（GLY；25.0%蛋白质；17.6 kJ/g，或4.2 kcal/g）或3%谷氨酰胺补充的固体饮食（GLN；25.0%蛋白质；17.6 kJ/g，或4.2 kcal/g），持续35天。将动物分为两组（血清甲氨蝶呤药代动力学，n = 20；或甲氨蝶呤肾脏清除，n = 16），并给予10 mg/kg剂量的甲氨蝶呤。与对照组相比，GLN组中甲氨蝶呤的平均总血清清除率降低了25%（分别为0.63±0.09 L·h-1·kg-1和0.47±0.13 L·h-1·kg-1，p = 0.01）。肾脏对甲氨蝶呤的清除减少了65%。两组之间甲氨蝶呤的分布容积或半衰期没有显著差异。谷氨酰胺降低了甲氨蝶呤的全身清除率，从而使宿主和肿瘤暴露于更高浓度的甲氨蝶呤中。
