Kühnel H J, Günther K, Stein G, Hoffmann-Traeger A
Institute of Clinical Pharmacology, Friedrich-Schiller-University Jena, GDR.
Int J Clin Pharmacol Ther Toxicol. 1987 Nov;25(11):616-21.
The pharmacokinetics and pharmacodynamics of repeated oral administration of furosemide were studied in patients with chronic renal failure or nephrotic syndrome using three different dosage regimens (4 x 40, 4 x 80 and 4 x 250 mg/d). Concentrations of the unchanged drug in serum and urine were measured fluorometrically. The elimination kinetics of furosemide was linear over the dose range studied. In contrast, the bioavailability of this diuretic decreased with increasing doses. The diuretic effects of all three dosage regimens were distinct only on the first day of therapy, thereafter decreasing rapidly. It can be concluded that the hormonal regulation of water and electrolyte balance are responsible for this behavior rather than pharmacokinetics. Creatinine and urea nitrogen excretion were not influenced by any furosemide dosage regimen.
采用三种不同给药方案（4×40、4×80和4×250mg/d），对慢性肾衰竭或肾病综合征患者反复口服呋塞米的药代动力学和药效学进行了研究。采用荧光法测定血清和尿液中未代谢药物的浓度。在所研究的剂量范围内，呋塞米的消除动力学呈线性。相比之下，这种利尿剂的生物利用度随剂量增加而降低。所有三种给药方案的利尿作用仅在治疗的第一天有明显差异，此后迅速下降。可以得出结论，水和电解质平衡的激素调节是导致这种现象的原因，而非药代动力学。任何呋塞米给药方案均未影响肌酐和尿素氮的排泄。
