Effect of Azole/Echinocandin Use on Tacrolimus Pharmacokinetics in Kidney Transplant Recipients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 507
- 试验地点
- 1
- 主要终点
- The C0/D values of tacrolimus
研究概览
简要总结
The purpose of this observational study is to analyze the extent and characteristics of drug interactions (focusing on azole antifungals and echinocandins) and genetic polymorphisms on tacrolimus blood concentrations in renal transplant recipients in order to provide a reference for the appropriate adjustment of tacrolimus dosing regimen to reduce the incidence of adverse drug reactions and rejection, and to improve the survival of transplanted kidneys.
详细描述
In this study, investigators investigated the effects of CYP3A5 and CYP2C19 gene polymorphisms on the trough concentration of tacrolimus after renal transplantation in recipients who were on a tacrolimus-based immunosuppressive regimen (tacrolimus + mescaline + glucocorticosteroid) after their first renal transplantation; investigators investigated the effects of antifungal drugs on the trough concentration of tacrolimus, and investigators also analyzed the effects of genetic factors on the drug-drug interactions between antifungal drugs and tacrolimus, with the aim of providing a basis of reference for the rational use of tacrolimus and antifungal drugs in the clinic.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with first kidney transplantation and intact CYP3A5 genotype;
- •Renal transplant recipients taking a tacrolimus-based triple immunosuppressive regimen (tacrolimus + sodium mescaline enteric-coated tablets + glucocorticoids) postoperatively;
- •Age ≥ 18 years.
排除标准
- •Missing and incomplete clinical information and postoperative follow-up data;
- •Multi-organ combined transplantation and secondary transplantation;
- •Postoperative simultaneous joint application of other drugs that affect the blood concentration of tacrolimus or voriconazole or caspofungin (e.g. pentoxifylline capsules, rifampicin, etc.);
- •Severe impairment of liver function or severe gastrointestinal diseases, gastrointestinal resection surgery, malabsorption syndrome;
- •Pregnant and lactating women;
- •Recipients with significant rejection of the transplanted organ or death due to other reasons within 1~2 months after surgery;
- •Poor compliance and accuracy of results (e.g., irregular blood collection times).
研究组 & 干预措施
Combined with voriconazole group
Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses. The starting dose of voriconazole should be 400 mg twice a day, which should be changed to 200 mg twice a day from the next day as a maintenance dose.
干预措施: Combined with voriconazole (Drug)
Combined with caspofungin group
Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses. The dosage of caspofungin was 70 mg intravenous injection once on the first day after surgery and 50 mg intravenous injection once a day starting from the second day.
干预措施: Combined with caspofungin (Drug)
Tacrolimus-alone treatment group
Methylprednisolone sodium succinate was administered intravenously the day after transplantation at an initial dose of 500 mg/day, with the dose being tapered evenly to 40 mg/day during the first week. During the second week, methylprednisolone tablets were administered continuously at a dose of 40 mg/day, after which the dose was tapered to 16 mg/day as a maintenance dose. Immunosuppression was maintained with oral mycophenolate sodium 720 mg twice daily. For renal transplant patients, the initial oral tacrolimus dose should be 0.15 - 0.30 mg/kg per day divided into morning and evening doses.
干预措施: Tacrolimus-alone treatment (Drug)
结局指标
主要结局
The C0/D values of tacrolimus
时间窗: 2015.01.01-2023.04.01
Body weight is in kilograms, D values are in mg/d, and the combination of body weight and D is the body weight-corrected D value in mg/kg/d, with a range of 0.15-0.30 mg/kg/d. The C0 for tacrolimus is in ng/ml, with a range of 5-15 ng/ml, and the combination of the C0 and body weight-corrected D values is the C0/D value, reported as (ng/ml)/(mg /kg/d) is reported.
次要结局
- The D values of tacrolimus(2015.01.01-2023.04.01)
研究者
LI YAN
director
Qianfoshan Hospital