Pharmacokinetic and pharmacodynamic study of febuxostat in hyperuricemia patients with chronic nephropathy
10.13699/j.cnki.1001-6821.2015.13.012
- VernacularTitle:非布司他在高尿酸血症伴慢性肾病患者中的药代动力学及药效学研究
- Author:
Hao-Wu HUANG
1
;
Ying-Bin HUANG
;
Huan-Wen HUANG
;
Chun-Zhong ZHOU
;
Pei-Qing LIN
Author Information
1. 珠海市人民医院 药学部
- Keywords:
febuxostat;
hyperuricemia;
chronic kidney disease;
pharmacokinetic;
pharmacodynamic
- From:
The Chinese Journal of Clinical Pharmacology
2015;(13):1258-1261
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the pharmacokinetic and pharmacody-namic characteristics of febuxostat tablets after single and mutiple oral dose in hyperuricemia patients with chronic kidney disease .Methods A total of 18 hyperuricemia patients with chronic kidney disease were ran-domly divided into three groups , each group containing 6 patients as fol-lows: those in group A were administrated with a single oral dose of febuxostat tablet 40 mg, those in group B were administrated with a single oral dose of febuxostat tablet 80 mg, and followed by multiple oral doses of febuxostat 80 mg, qd for 28 days and those in group C were treated with a single oral dose of febuxostat tablet 120 mg.The serum uric acid was determined by clinical chemistry testing , and the plasma drug levels were determined by HPLS -MS/MS method.Results The main febuxostat pharmacokinetic parameters of a single oral administra-tion of 40, 80 and 120 mg division were as follows: t1/2 were (3.98 ±1.45), ( 4.63 ±1.37 ) and ( 4.27 ±1.33 ) h; tmax were (0.97 ±0.39), ( 1.22 ±0.46 ), ( 1.35 ±0.37 ) h; Cmax were (1626.33 ± 342.97 ) , ( 2669.27 ± 384.91 ) , ( 3904.83 ± 835.98 ) ng ? mL-1; AUC0-24 h were (4324.32 ±976.87), (8415.4 ±1965.9), (12979.6 ±3788.5) ng? h? mL -1.Drug accumulation was not detec-ted following multiple oral doses .After 4 weeks treatment (80 mg, qd) , febuxostat lowered the serum uric acid levels of hyperuricemia patients with chronic kidney disease significantly , and the target serum uric acid level (6.0 mg? dL -1 ) was achieved in 5 patients.Conclusion Febuxostat displayed a linear pharmacokinetic profile in single oral doses of 40 to 120 mg.Continuous oral therapic dose of febuxostat tablets can significantly reduce the uric acid levels in hyperu -ricemia patients with chronic kidney disease .
