Jorkasky D K, Audet P, Shusterman N, Ilson B, Dafoe D, Hedrich D, Stote R M
Presbyterian Medical Center of Philadelphia, PA 19104.
Am J Kidney Dis. 1992 Jun;19(6):567-72. doi: 10.1016/s0272-6386(12)80836-5.
Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may contribute to chronic nephrotoxicity. This effect has not been consistently reversed by available pharmacologic agents. The efficacy of orally administered fenoldopam, a dopamine-1 (DA-1) agonist with renal vasodilator properties, was evaluated in six patients whose condition was stable 3 to 6 months following renal transplantation. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate (PAH) clearances, respectively, at baseline, after the acute oral administration of 100 mg of fenoldopam, and following 3 weeks of chronic oral fenoldopam therapy (100 mg thrice daily). Mean ERPF increased from 3.15 +/- 0.17 mL/s/1.73 m2 (189 +/- 10 mL/min/1.73 m2) at baseline to 3.48 +/- 0.17 mL/s/1.73 m2 (209 +/- 10 mL/min/1.73 m2) 4 hours after acute administration of fenoldopam (P = 0.04). Urine flow rate and fractional excretion of sodium also increased after acute administration, but not significantly. Mean systolic (SBP) and diastolic blood pressure (DBP) decreased maximally by 18 and 6 mm Hg, respectively, and mean pulse rate increased maximally by 8 bpm between 75 and 90 minutes after both acute and chronic administration. GFR was unchanged following both acute and chronic administration. The increase in ERPF was not maintained to the end of the dosing interval during chronic administration, probably due to the short half-life of fenoldopam. However, the renal vasodilatory response was still observed 3 to 4 hours after readministration of the drug following 3 weeks of oral dosing. Thus, fenoldopam significantly reverses the renal vasoconstriction caused by cyclosporine in renal transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
环孢素可引起肾血管收缩并减少肾血流量，这可能导致慢性肾毒性。现有药物制剂并不能始终如一地逆转这种效应。对6例肾移植后3至6个月病情稳定的患者评估了口服非诺多泮（一种具有肾血管舒张特性的多巴胺-1（DA-1）激动剂）的疗效。分别在基线、急性口服100 mg非诺多泮后以及慢性口服非诺多泮治疗3周（每日三次，每次100 mg）后，通过菊粉和对氨基马尿酸（PAH）清除率测量肾小球滤过率（GFR）和有效肾血浆流量（ERPF）。急性给予非诺多泮4小时后，平均ERPF从基线时的3.15±0.17 mL/s/1.73 m²（189±10 mL/min/1.73 m²）增加至3.48±0.17 mL/s/1.73 m²（209±10 mL/min/1.73 m²）（P = 0.04）。急性给药后尿流率和钠分数排泄也增加，但无显著差异。急性和慢性给药后，平均收缩压（SBP）和舒张压（DBP）分别最大降低18和6 mmHg，并在75至90分钟之间平均脉率最大增加8次/分钟。急性和慢性给药后GFR均未改变。慢性给药期间，ERPF的增加在给药间隔结束时未维持，可能是由于非诺多泮半衰期短。然而，在口服给药3周后再次给药后3至4小时仍观察到肾血管舒张反应。因此，非诺多泮可显著逆转肾移植受者中环孢素引起的肾血管收缩。（摘要截短至250字）
