Israel R, O'Mara V, Austin B, Bellucci A, Meyer B R
Clin Pharmacol Ther. 1986 Mar;39(3):261-4. doi: 10.1038/clpt.1986.36.
Intravenous dopamine has been shown to increase renal plasma flow in man. The role of endogenous dopamine in the maintenance of renal plasma flow has not been described. We speculated that if endogenous dopamine activity is important in the maintenance of renal plasma flow, then high doses of a potent dopamine blocking drug such as metoclopramide would decrease renal flow. To test this hypothesis, we measured renal plasma flow using a single-injection technique with 131I-labeled orthoiodohippurate. Measurements were made before and after the administration of high doses of metoclopramide (1 to 2.5 mg/kg) to 20 patients receiving metoclopramide as an antiemetic before chemotherapy. Seven control subjects underwent sequential measurements of renal plasma flow without intervening metoclopramide dosing. Mean (+/- SD) renal plasma flow did not change in the control population (from 441 +/- 198 to 437 +/- 117 ml/min), but declined significantly in the patients who received metoclopramide (443 +/- 115 ml/min before metoclopramide and 387 +/- 137 ml/min after metoclopramide; P less than 0.001). In 25% of our study population the decline in renal plasma flow was greater than 20% below baseline levels. The magnitude of the effect did not appear to correlate with the pretreatment creatinine clearance, age, or sex of the patients. We conclude that high doses of metoclopramide decrease renal plasma flow in man. These data suggest a role for dopamine in the maintenance of renal plasma flow in patients receiving intravenous hydration. Changes of the magnitude we observed may well be of clinical importance. These findings therefore also suggest the possibility of metoclopramide potentiation of cisplatin nephrotoxicity.
静脉注射多巴胺已被证明可增加人体肾血浆流量。内源性多巴胺在维持肾血浆流量中的作用尚未见描述。我们推测,如果内源性多巴胺活性在维持肾血浆流量中起重要作用,那么大剂量的强效多巴胺阻断药物(如甲氧氯普胺)会降低肾血流量。为验证这一假设,我们采用单次注射技术,使用131I标记的邻碘马尿酸盐来测量肾血浆流量。对20名在化疗前接受甲氧氯普胺作为止吐药的患者,在给予大剂量甲氧氯普胺(1至2.5毫克/千克)之前和之后进行测量。7名对照受试者在未给予甲氧氯普胺的情况下连续测量肾血浆流量。对照组的平均(±标准差)肾血浆流量没有变化(从441±198毫升/分钟降至437±117毫升/分钟),但接受甲氧氯普胺的患者肾血浆流量显著下降(甲氧氯普胺给药前为443±115毫升/分钟,给药后为387±137毫升/分钟;P<0.001)。在我们的研究人群中,25%的患者肾血浆流量下降超过基线水平的20%。这种效应的大小似乎与患者治疗前的肌酐清除率、年龄或性别无关。我们得出结论,大剂量甲氧氯普胺会降低人体肾血浆流量。这些数据表明多巴胺在接受静脉补液的患者维持肾血浆流量中起作用。我们观察到的这种程度的变化很可能具有临床重要性。因此,这些发现也提示了甲氧氯普胺增强顺铂肾毒性的可能性。