Influence of acute renal failure on the protein binding of drugs in animals and in man

Abstract

Serum protein binding of phenylbutazone has been measured in the rat, guinea pig, cat, rabbit and dog, and the influence on it of renal failure induced by uranyl nitrate injection has been studied. In all speciies a clearcut decrease in binding was observed after the occurrence of renal failure; the time course of the fall in binding correlated well with development of renal failure. In further experiments, serum protein binding of two acidic drugs (phenylbutazone, warfarin), two basic drugs (papaverine, quinidine) and one neutral drug (digitoxin) was studied in rabbits with experimental renal failure, and the results compared with those obtained in patients with acute renal failure. In the rabbits, a decrease in the binding of phenylbutazone, warfarin, papaverine and quinidine was found, whereas protein binding of digitoxin was unchanged. In man, there was a definite fall in protein binding of phenylbutazone and digitoxin, a small decrease for warfarin and papaverine, and a slight increase for quinidine.

Decreased Binding of Drugs and Dyes to Plasma Proteins From Rats With Acute Renal Failure: Effects of Ureter Ligation and Intramuscular Injection of Glycerol

“…1977). Glycerol-induced acute renal failure produced a statistically marginal decrease in warfarin binding which was more akin to the human results of Belpaire et al (1977) than to their findings for the rabbit.…”

“…Similarly, bilateral nephrectomy in the rat had no effect on either total plasma protein or albumin (Ghoneim et al, 1976). Renal failure in the rabbit (Taylor et al, 1954;Belpaire et al, 1977) and dog (Baker, 1951;Markievicz, Walasek, Trznadel & Lutz, 1974) also did not affect plasma albumin concentration. The likelihood that certain methods may underestimate the albumin content of Figure I Effect of dilution on the plasma protein binding of (a) o-methyl red (133 gM), (b) methyl orange (150 gM) and (c) phenytoin (39.6 gM) to normal male rat plasma at 37°C.…”

The effect of chronic renal failure on drug metabolism and transport

“…These effects may be partially reversed by dialysis. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. CYP activity in the kidney is estimated to be 20% of liver activity per gram of tissue.…”

“…Mechanisms point to circulating inhibitory factors some of which are dialyzable. Patients with advanced CRF Stage IV (GFR [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and Stage V (0-15 ml/min) may behave differently depending whether or not they are on dialysis since these factors may be partially removed by dialysis. Estimating the magnitude of these nonrenal effects is difficult without empirical studies.…”

Untersuchung der Wechselwirkung von Carbamazepin und Promazin mit Rinderserumalbumin mit Hilfe einer neuen Dialysevorrichtung

“…Die Literaturfülle der letzten zehn Jahre auf dem Gebiet der Bestimmung des freien Anteils eines Pharmakons in biologischem Material bietet hinsichtlich der angewandten Methoden ein einheitliches Bild: Benutzt wurden a) Gelfiltration (6-12) b) Gleichgewichtsdialyse (l 2-21) c) Ultrafiltration/-zentnfugation (12,(22)(23)(24)(25)(26)(27)(28)(29)(30) Ohne hier näher auf die Vor-und Nachteile der Gelund Ultrafiltration bzw. Ultrazentrifugation einzugehen (12), soll mit der vorliegenden Arbeit gezeigt werden, wie der wichtigste Nachteil der Gleichgewichtsdialyse, nämlich die Überlänge der Versuchsdauer (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) .…”