Morgant C, Contrepois A, Chau N P, Romaru A, Fourtillan J B, Carbon C
Antimicrob Agents Chemother. 1984 May;25(5):618-21. doi: 10.1128/AAC.25.5.618.
Antibiotics and diuretics are often prescribed concomitantly for humans. We compared the effects of two potent loop diuretics, furosemide and piretanide, with those of water loading on the urinary excretion of cefazolin. During a continuous infusion of inulin and cefazolin (10 mg/kg per h), six healthy male volunteers received a single intravenous injection of furosemide (0.3 mg/kg) or piretanide (0.1 mg/kg) or again an oral water load of 15 ml/kg over a 20-min period. In vitro, furosemide at all concentrations tested significantly reduced by about 10% the percentage of cefazolin bound to serum proteins. Piretanide exhibited such an effect only at a concentration of 2 micrograms/ml. Furosemide, piretanide, and water loading significantly and similarly increased the ratio of excreted to infused cefazolin up to 2 h after the injection of diuretic or after oral water intake. In each of the three parts of the experiment, the increase of the urinary flow rate was similar when compared with the control values. Furosemide significantly increased the cefazolin filtered load during the same time. Piretanide significantly enhanced the absolute rate of net cefazolin tubular secretion. Water loading increased the urinary excretion of cefazolin, probably through a reduction in tubular reabsorption. These results suggest that (i) furosemide and piretanide as well as water loading are capable of enhancing renal excretion of cefazolin by different complex mechanisms; (ii) cefazolin undergoes a bidirectional tubular transport; (iii) piretanide might act on the proximal tubule in addition to its main site of action on Henle's loop; and (iv) the effects of both diuretics and of water loading are unlikely to affect in vivo antibiotic activity in humans.
抗生素和利尿剂常常会同时给人类开具。我们比较了两种强效袢利尿剂（呋塞米和吡咯他尼）与水负荷对头孢唑林尿排泄的影响。在持续输注菊粉和头孢唑林（每小时10毫克/千克）期间，6名健康男性志愿者接受单次静脉注射呋塞米（0.3毫克/千克）或吡咯他尼（0.1毫克/千克），或者在20分钟内再次口服15毫升/千克的水负荷。在体外，所有测试浓度的呋塞米均使与血清蛋白结合的头孢唑林百分比显著降低约10%。吡咯他尼仅在浓度为2微克/毫升时才表现出这种作用。在注射利尿剂或口服水后长达2小时内，呋塞米、吡咯他尼和水负荷均显著且相似地增加了头孢唑林的排泄与输注比值。在实验的三个部分中，与对照值相比，尿流率的增加相似。呋塞米在同一时间显著增加了头孢唑林的滤过负荷。吡咯他尼显著提高了头孢唑林肾小管净分泌的绝对速率。水负荷增加了头孢唑林的尿排泄，可能是通过减少肾小管重吸收实现的。这些结果表明：（i）呋塞米、吡咯他尼以及水负荷能够通过不同的复杂机制增强头孢唑林的肾排泄；（ii）头孢唑林经历双向肾小管转运；（iii）吡咯他尼除了主要作用于髓袢外，可能还作用于近端小管；（iv）利尿剂和水负荷的作用不太可能影响人体内抗生素的活性。
