膜性腎症患者のFK506濃度に及ぼす武石ソフトカプセルの効果に関する臨床観察

Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients.

• Zhu Zhang
• Xiaobei Lu
• Leipeng Dong
• Jiwei Ma
• Xiaoguang Fan

抄録

本研究では、膜性腎症（MN）患者のFK506濃度とCYP3A5遺伝子多型との相関関係を調べることを目的とした。特発性MN患者75名を登録し、CYP3A5遺伝子代謝酵素の発現状況によりA群（CP3A5代謝酵素機能発現型CYP3A5*1/*1型、CYP3A5*1/*3型）とB群（非発現型CYP3A5*3/*3型）に分けた。全例にタクロリムスカプセルの初回投与量1"Zs_200A"mgを1日2回、朝食前と夕食前に1"Zs_200A"時間経口投与した。その後、3食後30分以内にWZCを0.5"Zs_200A"gとして1日3回経口投与したところ、A群及びB群のFK506の血中濃度は投与前に比べて有意に高かった。A群及びB群のFK506の血中濃度は投与前と比較して有意に高く、WZC添加後のFK506の血中濃度は3.051"Zs_200A"±"Zs_200A"0.774 ng/ml増加した。また、A群のFK506の血中濃度は、投与前後のB群よりも低く、一方、24時間の総尿蛋白及び生化学的指標は、両群とも統計的に有意な差は認められなかった。また、下痢は1例のみで、タクロリムスを減量した後に緩和されました。また、FK506の血中濃度を上昇させるためにWZCを使用する場合には、CYP3A5遺伝子型を考慮する必要があります。

The current research aimed to investigate the correlation between the effect of Wuzhi soft capsule (WZC) on FK506 concentration and CYP3A5 gene polymorphism in patients with membranous nephropathy (MN).Seventy-five patients with idiopathic MN were enrolled and divided according to the expression of CYP3A5 gene metabolic enzyme into group A (CP3A5 metabolic enzyme function expression types CYP3A5*1/*1 type and CYP3A5*1/*3 type), and group B (non-expression type CYP3A5*3/*3 type). All patients were given oral administration of tacrolimus capsule at the initial dose of 1 mg for twice a day 1 hour before breakfast and dinner. Afterwards, the oral administration of WZC was added at the dose of 0.5 g for 3 times a day within half an hour after 3 meals.The blood concentrations of FK506 in groups A and B were significantly higher than those before administration. Compared with that before administration, the FK506 blood concentration was increased by 3.051 ± 0.774 ng/ml after adding the WZC. Besides, the blood concentrations of FK506 in group A were lower than those in group B before and after administration; meanwhile, the 24 hours total urine protein and the biochemical indexes in both groups displayed no statistically significant difference. Only 1 case of diarrhea was observed, which was relieved after the reduction of tacrolimus.Wuzhi soft capsule can significantly increase the blood concentration of FK506 in MN patients. Moreover, the CYP3A5 genotyping should be considered when WZC is used to increase the blood concentration of FK506.