Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine infusion, when commenced 24 h after the insult, was ineffective in modifying the course of uranyl nitrate induced renal failure in rabbits.
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PMID:Preliminary observations concerning the effect of dopamine on uranyl nitrate induced renal failure. 52 Apr 79

Pharmacokinetic studies were conducted in 8 patients with disseminated neoplasms refractory to conventional chemotherapy, who received gallium nitrate at doses of 300 to 600 mg/m2 intravenously in a phase I clinical trial. Gallium concentrations in biological fluids were determined colorimetrically. In patients with normal renal function, gallium showed a biphasic plasma disappearance with an initial half-life (t1/2) of 0.5 to 1.8 hr (mean 1.0) and a terminal t1/2 of 10.5 to 50.4 hr (mean 25.1). Gallium was distributed in total body water and often localized in some body compartment as evidenced by a volume of distribution ranging from 0.25 to 2.53 L/kg (mean 1.19). The total drug clearance from the plasma was 0.13 to 1.00 ml/kg/min (mean 0.65) in patients with normal renal function. Cumulative urinary excretion of gallium was 15% to 72% (mean 35%) of the administered dose in 24 hr (it fell to 23% in 8 days in a patient with acute oliguric renal failure). Gallium kinetics are altered in patients with acute renal dysfunction and in patients who have received multiple doses of gallium or other metal chemotherapy.
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PMID:Kinetics of gallium nitrate, a new anticancer agent. 75 46

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.
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PMID:Influence of acute renal failure on the protein binding of drugs in animals and in man. 83 54

Quinidine serum binding is increased in some patients with acute renal failure, but in animals with renal failure conflicting results were published. Therefore, serum binding of quinidine, papaverine and phenylbutazone was studied by equilibrium dialysis in rabbits and rats with acute renal failure induced either by injection of uranyl nitrate or ligation of the ureters. From the results it appears that, in animals, quinidine binding changes are different according to the model used for induction of the renal failure, regardless of the species studied. After ligation of the ureters, lipoprotein concentration increases, but the meaning of this increase for increased serum quinidine binding is not clear.
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PMID:Serum binding of quinidine in experimental acute renal failure. 89 46

In an attempt to alter the natural course of glycerol and uranyl nitrate induced acute ranal failure in the rat, the vasodilator, prostaglandin A1 was adminstered systemically at varying times during the induction phase of renal failure. According to the method used, no significant beneficial effect could be demonstrated in either experimental model.
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PMID:Effect of prostaglandin a1 on acute renal failure in the rat. 112 55

The effect of renal failure upon the "in vitro" binding of midazolam, a new water-soluble short-acting benzodiazepine, has been studied in man. An increase of its free fraction (ranging from 2.52 to 5.17%) in serum from uremic patients was observed. A similar situation was originated in rabbits by administering uranyl nitrate (2 mg/Kg i.v.) and posterior hypnosis with midazolam. Uremic rabbits showed a marked increase in the free concentration of midazolam in serum (ranging from 8.9 to 13.7 micrograms/ml) and in midazolam brain levels (156.2 micrograms/g in cortex vs 84.5 micrograms/g in control animals). A positive correlation between brain and serum free concentration of midazolam was also observed. It is concluded that in renal patients more unbound drug is available to produce central nervous system effects, and a decrease in intravenous dose of midazolam could be recommended in this clinical situation.
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PMID:The influence of renal failure on the kinetics of intravenous midazolam: an "in vitro" and "in vivo" study. 147 30

Erythrocyte structure was studied in rat after uranyl nitrate (UN:5 mg/kg) intoxication. The study of pathogenic progression of UN induced renal failure (ARF) was confined to the early initiation phase (2 hr), late initiation phase (8 hr) and the maintenance phase (24 hr). Erythrocyte structure has been found to be greatly influenced. The UN induced hemolytic syndrome/hypoxia was accompanied by a marked anisocytosis and poikilocytosis during different phases of ARF, which is characteristic of UN poisoning. Subsequent alterations in erythrocyte structure followed by UN administration or during the pathogenic progression of ARF has clinical and diagnostic importance as the alterations were much distinct prior to the clinical manifestation of ARF even at light microscopic level.
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PMID:Uranyl nitrate induced corpuscular derangement: an early indication of induced acute renal failure. 152 60

The brain uptake of a number of benzodiazepines with different lipophilic and protein binding characteristics was investigated in male Sprague-Dawley rats using the rapid intracarotid artery injection technique. When the compounds were administered as a solution in Ringer's buffer, pH 7.4, the uptake was in the order of [14C]diazepam greater than [14C]L-663,581 (anxiolytic agent) greater than [3H]L-364,718 (morphine analgesia potentiator) greater than [14C]L-365,260 (anxiolytic agent) and their extraction ratio values were 71.0 +/- 6.8, 65.0 +/- 12.0, 42.0 +/- 5.0 and 6.0 +/- 2.0%, respectively. The respective permeability-surface product values were 0.755 +/- 0.152, 0.647 +/- 0.180, 0.329 +/- 0.05 and 0.035 +/- 0.011 ml/min/g. The rank order of brain extraction did not correlate well with the drugs' lipophilicity determined by octanol-buffer partition coefficient. For example, L-365,260 had the highest octanol/buffer partition coefficient, but the lowest brain extraction. Plasma protein binding significantly decreased the uptake by the brain but to a lesser extent than that predicted from the unbound drug fraction in vitro, suggesting that drug binding to plasma protein did not limit the transport of drug through the blood-brain barrier. For one compound, L-364,718, the extraction ratio and permeability-surface product values were increased markedly in CC1(4)-induced hepatic injury. Other disease states, uranyl nitrate-induced renal failure and streptozotocin-induced diabetes, had no apparent effect on the uptake of the compounds tested. The effect of disease state on the brain uptake of drug appeared to be dependent on the type of disease and the type of drug studied.
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PMID:Effects of protein binding and experimental disease states on brain uptake of benzodiazepines in rats. 197 Mar 63

The effect of oral administration of activated charcoal on total body clearance of gentamicin administered intravenously (2 mg kg-1) has been studied in normal rabbits and rabbits with induced renal failure. Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits produced a significant reduction in gentamicin serum concentrations compared to control. Significant differences between treated and control groups, compatible with enhancement of gentamicin elimination, were observed in the calculated pharmacokinetic parameters (Kel, t 1/2, CL and AUC). To examine whether renal failure could augment the effect of activated charcoal in enhancing the systemic clearance of gentamicin, uranyl nitrate was used (0.75 mg kg-1, i.v.) to induce acute renal failure in rabbits. The derived pharmacokinetic parameters of gentamicin during the control phase in these animals were consistent with severe renal failure. The administration of activated charcoal, 2.5 h following gentamicin injection, produced a steeper decline in gentamicin concentration-time profiles and significant changes in Kel, t 1/2 and CL. The Kel and CL values increased to about 200%, while the t 1/2 value decreased to about 50%. The apparent changes in the pharmacokinetic parameters induced by charcoal administration were more marked in rabbits with renal failure than in normal rabbits; however, induction of renal failure did not augment the charcoal-induced clearance of gentamicin quantitatively.
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PMID:The effect of oral activated charcoal on the systemic clearance of gentamicin in rabbits with acute renal failure. 197 7

The characteristics of exsorption and/or excretion of procainamide and its metabolite, N-acetylprocainamide (NAPA), into the small intestinal lumen in both normal rats and rats with acute renal failure (ARF rats) induced by uranyl nitrate were investigated by an in situ single-pass perfusion technique. The exsorption of procainamide and NAPA from blood into the intestinal lumen was increased in ARF rats compared with normal rats. The mean apparent renal, biliary and intestinal clearance values of procainamide were 186, 1.83 and 73.9 ml/h/kg in normal rats, respectively, and were 2.02, 1.37 and 55.8 ml/h/kg in ARF rats respectively. Furthermore, the mean renal, biliary and intestinal clearance values of NAPA were 35.2, 19.4 and 21.1 ml/h/kg in normal rats, respectively, and were 1.12, 21.0 and 26.0 ml/h/kg in ARF rats, respectively. There was little difference in the intestinal clearance values of procainamide and NAPA between normal and ARF rats. The ratio of nonrenal clearance/total body clearance was greater in ARF rats than in normal rats. Treatment with oral activated charcoal reduced the serum NAPA levels in both normal and ARF rats, and had little effect on the serum procainamide levels in normal rats, while it reduced the serum drug levels in ARF rats. Consequently, the increase in both drugs transported into the intestinal lumen induced by renal failure may enhance the intestinal clearance of the drug by oral administration of activated charcoal.
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PMID:Transport of procainamide and N-acetylprocainamide from blood into the intestinal lumen and intestinal dialysis by oral activated charcoal in rats with acute renal failure. 246 Jun 13


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