胡超 1梁茂植 1郑静 1苗佳 1刘芳 2胡婷婷 3顾景凯 4舒世清 1王颖 1朱晓红1
作者信息
- 1. 四川大学华西医院Ⅰ期临床研究室 成都610041
- 2. 四川大学华西医院肾内科 成都610041
- 3. 成都军区总医院临床药学科 成都610083
- 4. 吉林大学药物代谢研究中心 长春130000
- 折叠
摘要
Abstract
Objective To compared the differences in pharmacokinetics of phosphate retagliptin tablets in patients with varying degrees of renal dysfunction.Methods A total of 32 patients were categorized into five groups according to their renal function:normal,mild dysfunction,moderate dysfunction,severe dysfunction,and end stage renal dysfunction (ESRD).All of the patients took a single dose of 50 mg phosphate retagliptin tablet.Their plasma and urinary concentrations of phosphate retagliptin (SP2086) and phosphate retagliptin acid (SP2086 acid) were determined using LC-MS/MS methods.The plasma pharmacokinetic parameters were calculated using WinNolin 6.1 software.Results Peak concentrations (Cmax) of SP2086 reached at (1.07±0.35) h in the patients with mild renal dysfunction,(1.50±0.89) h in the patients with moderate renal dysfunction,(1.67±2.16) h in the patients with severe renal dysfunction,(2.42±2.15) h in the patients with ESRD,and (1.75±1.21) h in the normal participants,with a clearance (CL/F) of (23.50±6.01),(12.90±4.34),(6.70±1.55),(3.10±0.48),and (30.50±10.70) L/h,respectively.With the increasing damages in renal function presented an incease in C time to reach Cmax (Tmax),and area under curve (AUC),a decrease in CL/F,of SP2086 and SP2086 acid.The 0-96 h urine cumulative excretion percentage (Ae％) of SP2086 ranged from 0.441％ to 4.530％.The Ae％ of SP2086 acid reached (71.7±14.3)％± in the patients with mild renal dysfunction,(59.5 ± 22.7)％ in the patients with moderate renal dysfunction,(63.3±13.9)％ in the patients with severe renal dysfunction,(34.1±20.0)％ in the patient with ESRD,and (74.2 ± 14.6)％ in the normal participants,with a renal clearance (CLR) of (220.0 ± 51.2),(105.0±64.5),(54.5±7.6),(13.5±7.8),and (289.0±73.7) mL/min,respectively.Compared with the participants with normal renal function,the AUCs of SP2086 and SP2086 acid were 1.44 times and 2.32 times higher in the patients with moderate renal dysfunction,2.20 times and 4.39 times higher in the patients with severe renal dysfunction,and 2.83 times and 9.28 times higher in the patients with ESRD.Conclusion The dosage of phosphate retagliptin tablet is recommended at 100 mg/d for patients with normal renal function and those with mild renal dysfunction,at 50 mg/d for patients with moderate renal dysfunction,and at 25 mg/d for patients with severe renal dysfunction.No phosphate retagliptin tablet is recommended for patients with ESRD.关键词
磷酸瑞格列汀/肾功能不全/药代动力学/剂量调整Key words
Phosphate retagliptin/Renal dysfunction/Pharmacokinetics/Dose adjustment
