Altered furosemide pharmacokinetics in chronic alcoholic liver disease with ascites contributes to diuretic resistance.
Altered furosemide pharmacokinetics in chronic alcoholic liver disease with ascites contributes to diuretic resistance.
复制标题
慢性酒精性肝病腹水患者中呋塞米药代动力学的改变会导致利尿剂抵抗。
DOI：
10.1016/0016-5085(87)90120-x
复制
发表时间：
1987
期刊：
影响因子：
29.4
通讯作者：
Zipser,RD
中科院分区：
文献类型：
--
作者：
Pinzani,M;Daskalopoulos,G;Laffi,G;Gentilini,P;Zipser,RD
一些慢性酒精性肝病和腹水患者对呋塞米的利钠反应受损。为了阐明这种利尿剂抵抗的机制，我们在26例患者静脉注射80 mg呋塞米后测定了对氨基马尿酸和菊粉的清除率以及电解质、前列腺素E2和呋塞米的尿排泄。利钠反应是可变的（3.3-172 mEq/h），与基础钠排泄、肾脏清除率或尿前列腺素E2无关。尿钠与血浆醛固酮呈负相关（r =-0.54，p < 0.01），与尿呋塞米呈强相关（范围5.5-76 mg/h，r = 0.71，p < 0.001）。由于尿呋塞米排泄反映了到达肾小管腔侧活性部位的呋塞米量，因此数据表明利尿剂抵抗患者主要作用部位的呋塞米量显著减少。血浆呋塞米水平在呋塞米排泄减少和尿钠排泄受损的患者中更高，这表明缺陷是呋塞米转运到肾小管的障碍。因此，利尿剂抵抗的一个主要因素是呋塞米药代动力学的改变。
Some patients with chronic alcoholic liver disease and ascites have an impaired natriuretic response to furosemide. To elucidate the mechanism of this diuretic resistance, we measured para-aminohippurate and inulin clearances and urinary excretion of electrolytes, prostaglandin E2, and furosemide after intravenous administration of 80 mg of furosemide in 26 patients. The natriuretic response was variable (3.3–172 mEq/h) and was unrelated to basal sodium excretion, renal clearances, or urinary prostaglandin E2. Natriuresis correlated negatively with plasma aldosterone (r = −0.54, p < 0.01), and strongly with urinary furosemide (range 5.5–76 mg/h, r = 0.71, p < 0.001). As urinary furosemide excretion reflects the amount of furosemide reaching the active site on the luminal side of the tubule, the data demonstrate markedly reduced amounts of furosemide at its primary site of action in patients with diuretic resistance. Plasma furosemide was higher in patients with reduced furosemide excretion and impaired natriuresis, suggesting that the defect was an impairment of furosemide transport into the tubule. Thus, a major factor in diuretic resistance is altered furosemide pharmacokinetics.