一名具有20年3级高血压病史的71岁男性在2年前出现肾功能不全。当时他的血清肌酐(SCr)为140μmol/L[估计肾小球滤过率(eGFR)为43.9ml/min/1.73m2],此后他接受了厄贝沙坦。在最初的介绍中,斑点尿液试纸蛋白为1+,白蛋白与肌酐的比率为230mg/g(0-30),尿液沉积物正常。SCr为176μmol/L(eGFR=32.8ml/min/1.73m2)。尽管从2个月前开始每天两次口服琥珀酸亚铁100mg,但血红蛋白(Hb)水平从102g/L降至96g/L。Roxadustat(ROXA)50毫克(体重,70kg),然后每周三次。不幸的是,患者错误地每天三次服用50毫克的药物(即,1,050毫克,而不是每周预期的150毫克),这是非透析依赖性慢性肾脏病(CKD)患者推荐起始剂量的3.5倍(体重>60kg,每周100mg3次),是该国批准的手册推荐每周最高剂量(每周2.5mg/kg3次)的两倍.当主治肾脏科医生在1个月后发现误用时,患者报告没有明显的不适,他的家庭血压在110-130/60-80mmHg范围内。重复血液测试显示,一个月内Hb从96增加到163g/L,SCr从199增加到201μmol/L。血清丙氨酸转氨酶(ALT)保持在正常范围内(从基线时的12U/L到20U/L),而血清总胆红素和间接胆红素水平略有升高。ROXA立即被扣留。在30天内,血清胆红素恢复到基线,但是Hb从163下降到140g/L,3个月后至108g/L。另一方面,SCr从179增加到203μmol/L。初次给药后9个月,当SCr增加到256μmol/L,Hb再次降低到94g/L时,ROXA50mg,每周3次,顺利重新启动。在这里,通过介绍一个在一个月内错误地服用了两倍最高推荐剂量的ROXA的病例,但显然没有明显的不适或不利的后果,我们试图提供作用机制的简要概述,特点,药物代谢,以及与该药物相关的副作用概况。
A 71-year-old man with a 20-year history of grade 3 hypertension experienced kidney dysfunction 2 years earlier. His serum creatinine (SCr) at the time was 140 μmol/L [with estimated glomerular filtration rate (eGFR) of 43.9 ml/min per 1.73m2], for which he received irbesartan since. At initial presentation, the spot urine dipstick protein was 1+, with an albumin-to-creatinine ratio of 230 mg/g (0-30) and normal urine sediments. The SCr was 176 μmol/L (eGFR = 32.8 ml/min per 1.73m2). The hemoglobulin (Hb) level decreased from 102 to 96 g/L despite oral ferrous succinate 100 mg twice daily starting 2 months ago. Roxadustat (ROXA) 50 mg (body weight, 70 kg) three times weekly was then prescribed. Unfortunately, the patient mistakenly took the drug at 50 mg three times a day (i.e., 1,050 mg instead of the intended 150 mg per week), which was 3.5 times the recommended starting dose for non-dialysis-dependent chronic kidney disease (CKD) patients (100 mg three times weekly for body weight >60 kg) and two times the highest drug manual-recommended weekly dose (2.5 mg/kg three times weekly) approved in the country. When the attending nephrologist discovered the misuse 1 month later, the patient reported no apparent discomfort, and his home blood pressure was in the range 110-130/60-80 mmHg. Repeat blood tests showed that the Hb increased from 96 to 163 g/L and the SCr from 199 to 201 μmol/L in a month. The serum alanine transaminase (ALT) remained within the normal range (from 12 U/L at baseline to 20 U/L), while the serum total and indirect bilirubin levels were slightly elevated. ROXA was withheld immediately. In 30 days, the serum bilirubin returned to baseline, but the Hb decreased from 163 to 140 g/L, and then to 108 g/L after 3 months. On the other hand, the SCr increased from 179 to 203 μmol/L. At 9 months after the initial dosing, when the SCr increased to 256 μmol/L and the Hb decreased to 94 g/L again, ROXA 50 mg three times weekly was reinitiated uneventfully. Herein, by introducing a
case who erroneously consumed twice the highest recommended dose of ROXA for a month, but had apparently no obvious discomfort or unfavorable consequence, we attempt to provide a brief overview of the mechanism of action, characteristics, drug metabolism, and side effect profile associated with this agent.