终末期肾病患者活体肾移植后 OATP1B 活性的恢复。
Recovery of OATP1B Activity after Living Kidney Transplantation in Patients with End-Stage Renal Disease.
机构信息
Department of Clinical Pharmacy, Oita University Hospital, 1-1 Hasama-machi, Oita, 879-5593, Japan.
Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan.
出版信息
Pharm Res. 2019 Feb 26;36(4):59. doi: 10.1007/s11095-019-2593-8.
PURPOSE
Recently, several studies have shown that renal failure decreases the metabolic clearance of drugs and the transportation capability of some drug transporters. However, whether organic anion transporting polypeptide (OATP)1B activities decrease in renal failure remains unknown. In this study, we measured plasma concentrations of coproporphyrin-I (CP-I), a specific endogenous OATP1B probe, in patients with end stage renal disease before and after living kidney transplantation and evaluated the effect of renal function on OATP1B activity.
METHODS
This prospective study recruited 13 patients with end-stage renal disease. Plasma CP-I concentrations were measured before and 7, 14, 30 and 90 days after living kidney transplantation.
RESULTS
Plasma CP-I concentrations decreased over time after living kidney transplantation and showed significant difference on day 90 compared with before living kidney transplantation [1.12 ± 0.59 vs 0.65 ± 0.27 ng/mL, p < 0.05 (95% CI of difference - 0.927, -0.013)]. A significant negative correlation was observed between estimated glomerular filtration rate and plasma CP-I concentration (r = -0.30, p < 0.05), suggesting recovery of OATP1B activity with improvement in renal function.
CONCLUSIONS
OATP1B activity may decrease in renal failure and dose adjustment of OATP1B substrates may be needed in patients with renal failure.
目的
最近有几项研究表明，肾衰竭会降低药物的代谢清除率和某些药物转运体的转运能力。然而，肾衰竭是否会降低有机阴离子转运多肽（OATP）1B 的活性尚不清楚。在本研究中，我们测量了终末期肾病患者活体肾移植前后血浆中粪卟啉 I（CP-I）的浓度，CP-I 是一种特定的内源性 OATP1B 探针，并评估了肾功能对 OATP1B 活性的影响。
方法
这项前瞻性研究纳入了 13 名终末期肾病患者。在活体肾移植前以及移植后 7、14、30 和 90 天测量血浆 CP-I 浓度。
结果
活体肾移植后 CP-I 浓度随时间逐渐降低，与活体肾移植前相比，第 90 天差异有统计学意义[1.12±0.59 比 0.65±0.27ng/mL，p<0.05（差值 95%CI：-0.927，-0.013）]。估算肾小球滤过率与 CP-I 浓度呈显著负相关（r=-0.30，p<0.05），提示随着肾功能的改善，OATP1B 活性恢复。
结论
肾衰竭可能会降低 OATP1B 活性，肾衰竭患者可能需要调整 OATP1B 底物的剂量。
Zotero 插件