Moulin B, Vernillet L, Dadoun C, Le Bigot J F, Godin M, Fillastre J P
Service de néphrologie, CHU Rouen, Hôpital de Bois-Guillaume.
Nephrologie. 1989;10(1):17-22.
The pharmacokinetics of Cy A have been studied in patients with N.S.. Eight patients (7 M, 1 F) received a single 12.5 mg/kg oral dose and a single 4 mg/kg intravenous dose. Plasma was separated from red blood cells at 22 degrees C, at least 2 hr after drawing. Cy A plasma levels were determined by reverse HPLC. The comparison of our pharmacokinetic parameters for the oral route with those from reference patients showed significant differences for T1/2 Ka and Tmax which were decreased in N.S. For the I.V. route we found a decrease in total plasma clearance (CLTP). Absolute bioavailability (18%) was also diminished. Moreover total cholesterol and B apolipoprotein were increased in our nephrotic population. Cy A is highly bound to lipoprotein and we found a significant negative correlation between CLTP of Cy A and either B apolipoprotein or total cholesterol. We conclude that the increase of lipoprotein in N.S. is probably responsible of the modifications in pharmacokinetics of Cy A. Nevertheless Cy A dosage can be not modified in N.S. when oral route is used and divided by a factor two for the I.V. route.
已对患有肾病综合征（N.S.）的患者进行了环孢素A（Cy A）的药代动力学研究。8名患者（7名男性，1名女性）接受了单次12.5 mg/kg的口服剂量和单次4 mg/kg的静脉注射剂量。在抽血后至少2小时，于22摄氏度下将血浆与红细胞分离。通过反相高效液相色谱法测定Cy A的血浆水平。将我们口服途径的药代动力学参数与参考患者的参数进行比较，发现N.S.患者的T1/2 Ka和Tmax存在显著差异，均有所降低。对于静脉注射途径，我们发现总血浆清除率（CLTP）降低。绝对生物利用度（18%）也降低了。此外，我们的肾病患者群体中总胆固醇和载脂蛋白B升高。Cy A与脂蛋白高度结合，我们发现Cy A的CLTP与载脂蛋白B或总胆固醇之间存在显著的负相关。我们得出结论，N.S.患者中脂蛋白的增加可能是Cy A药代动力学改变的原因。然而，当采用口服途径时，N.S.患者的Cy A剂量可不作调整，而静脉注射途径的剂量则除以2。
