Acarbose應用於第二型糖尿病合併腎衰竭患者之可能禁忌機轉

Possible Mechanism of Contraindication to Acarbose in Type 2 Diabetic Patients with Renal Failure

陳銘鴻(Ming-Hong Chen) ； 康玉嬋(Yu-Chan Kang) ； 王佩文(Pei-Wen Wang)

《內科學誌》 20卷5期 (2009/10) Pp. 434-439

https://doi.org/10.6314/JIMT.2009.20(5).07

摘要

In Taiwan, 25.7% of dialysis patients have diabetes mellitus and more than 39.8% of patients with type-2 diabetes have microalbuminuria. Despite of this fact, 93.3% of type-2 diabetes patients are treated with oral antidiabetic drugs (OADs), leading to great interest in relative drug metabolic disturbance caused by nephropathy. The prescribing rate in Taiwan for acarbose rose from 0.02% in 1997 to 4.1% in 2003 (P＜0.0001). However, the safety of using acarbose has frequently been ignored in diabetic patients with nephropathy. In healthy volunteers with normal renal function, only 1.7% of an oral dose of acarbose was absorbed as an original compound. However, approximately 35% of the ingested dosage marked with 14C was recovered in urine, indicating that its metabolites have been absorbed. In populations with renal impairment (creatinine clearance＜25 ml/min), the values of the peak plasma concentration and the mean steady-state area under the curve (AUC) of acarbose increased by five and six times normal values, respectively. Although there currently does not exist evidence that acarbose is toxic to the kidney, acarbose and its metabolites very likely accumulate in the patients with renal impairment, causing ill-defined iatrogenic risks. In related clinical trials, significant increases in transaminases were found in 3.8~15% of patients treated with acarbose. However, the latent period of acarbose induced hepatoxicity may last up to weeks or months after ingestion and without any allergic reactions. Therefore, the mechanism of acarbose induced hepatoxicity, caused by the original compound or its metabolites, may be due to metabolic idiosyncrasy. Although there are no available clinical trial data or case reports of hepatotoxicity in the patients with renal impairment, it is reasonable to be aware of accumulation of the drug and its metabolites in particular, in such patients, as well as those with high incidence of liver abnormalities. The use of acarbose is therefore contraindicated in patients with severe renal failure. Lower dosage and enzyme monitoring are recommended for those who must be treated with acarbose.

關鍵字

第二型糖尿病 ； 糖尿病腎病變 ； Acarbose ； 肝毒性

並列摘要

In Taiwan, 25.7% of dialysis patients have diabetes mellitus and more than 39.8% of patients with type-2 diabetes have microalbuminuria. Despite of this fact, 93.3% of type-2 diabetes patients are treated with oral antidiabetic drugs (OADs), leading to great interest in relative drug metabolic disturbance caused by nephropathy. The prescribing rate in Taiwan for acarbose rose from 0.02% in 1997 to 4.1% in 2003 (P＜0.0001). However, the safety of using acarbose has frequently been ignored in diabetic patients with nephropathy. In healthy volunteers with normal renal function, only 1.7% of an oral dose of acarbose was absorbed as an original compound. However, approximately 35% of the ingested dosage marked with 14C was recovered in urine, indicating that its metabolites have been absorbed. In populations with renal impairment (creatinine clearance＜25 ml/min), the values of the peak plasma concentration and the mean steady-state area under the curve (AUC) of acarbose increased by five and six times normal values, respectively. Although there currently does not exist evidence that acarbose is toxic to the kidney, acarbose and its metabolites very likely accumulate in the patients with renal impairment, causing ill-defined iatrogenic risks. In related clinical trials, significant increases in transaminases were found in 3.8~15% of patients treated with acarbose. However, the latent period of acarbose induced hepatoxicity may last up to weeks or months after ingestion and without any allergic reactions. Therefore, the mechanism of acarbose induced hepatoxicity, caused by the original compound or its metabolites, may be due to metabolic idiosyncrasy. Although there are no available clinical trial data or case reports of hepatotoxicity in the patients with renal impairment, it is reasonable to be aware of accumulation of the drug and its metabolites in particular, in such patients, as well as those with high incidence of liver abnormalities. The use of acarbose is therefore contraindicated in patients with severe renal failure. Lower dosage and enzyme monitoring are recommended for those who must be treated with acarbose.

並列關鍵字

Type 2 diabetes ； Diabetic nephropathy ； Acarbose ； Hepatotoxicity