dexloxiglumide的药动学特征。

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D’amato M Persiani年代,Jakate,罗伊·P Wangsa J, Kapil R, Rovati LC

dexloxiglumide的药动学特征。

Pharmacokinet。2006; 45 (12): 1177 - 88。

PubMed ID
17112294 (在PubMed
]
文摘

Dexloxiglumide是一个强有力的和选择性缩胆囊素1型(CCK1受体拮抗剂)目前正在开发的各种疾病影响gastro-oesophageal回流等胃肠道疾病,肠易激综合症(IBS),功能性消化不良,便秘和胃排空障碍。女性constipation-predominant IBS患者临床疗效已经证明后管理dexloxiglumide 200毫克每日三次。Dexloxiglumide单一口服后迅速而广泛地吸收人类的绝对生物利用度为48%。不完整的生物利用度是由于不完全吸收和肝脏初步的效果。后multiple-dose管理200毫克每日三次,积累是可预测的,表明长期有效的药物动力学。此外,dexloxiglumide药物动力学后dose-independent单一和重复口服每日三次剂量的剂量范围100 - 400毫克。Dexloxiglumide吸收窗口扩展从空肠结肠和药物是22的底物和抑制剂疲软和多药耐药性蛋白质1。dexloxiglumide是94 - 98%的血浆蛋白结合的药物有温和低体积分布在人类身上。系统性间隙dexloxiglumide适中和细胞色素P450 (CYP) 3 a4/5和CYP2C9涉及dexloxiglumide的新陈代谢产生O-demethyl dexloxi-glumide。这种代谢物进一步氧化dexloxiglumide羧酸。 These two major metabolites (accounting for up to 50% of dexloxiglumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive. In addition, the drug is a single isomer chiral drug (eutomer) that does not undergo chiral inversion into its pharmacologically inactive enantiomer (distomer). After oral administration of (14)C-dexloxiglumide, radioactivity is mainly excreted in bile and in faeces (74% of dose) with much lower excretion in urine (20% of dose). Renal excretion of unchanged dexloxiglumide is low (7% of dose in urine and faeces, 1% of dose in urine) and is dose-independent in the dose range 100-400 mg. As the kidney is a minor contributor to the elimination of dexloxiglumide and/or its metabolites in humans, the pharmacokinetics of the drug should not be affected in patients with renal insufficiency. The pharmacokinetics of dexloxiglumide are also not affected by age, sex and administration with a high-fat breakfast. Mild and moderate liver impairment do not affect the pharmacokinetics of dexloxiglumide but severe liver impairment causes increases in systemic exposure to dexloxiglumide and O-demethyl dexloxiglumide. Thus, the drug should be prescribed with caution in patients with severe hepatic impairment even though no dose adjustment is warranted. The results of different drug interaction studies have indicated that no clinically relevant metabolic and concomitant drug-drug interactions are expected during the clinical use of dexloxiglumide.

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药物
药物靶点
药物 目标 类 生物 药理作用 行动
Dexloxiglumide 缩胆囊素受体类型 蛋白质 人类
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