Excretion Of Nicotinic Acid Research Articles

Gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin in healthy Chinese volunteers

The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.

A comparison of the pharmacokinetics of two different formulations of extended-release niacin

ABSTRACTObjective: The objective of this study was to compare pharmacokinetic parameters of niacin extended-release tablets (NER uncoated) and niacin extended-release caplet formation (NER coated).* Niaspan is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA† Niaspan CF is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USAResearch design and methods: Twenty-five healthy male and female subjects were enrolled in a four-period, open-label, randomized, crossover study. Both NER uncoated and NER coated were given as 1 × 1000 mg or 2 × 500 mg tablets. Similarity of NER coated 1 × 1000 mg and NER uncoated 2 × 500 mg was declared if 90% confidence intervals for the geometric mean ratio (GMR) for nicotinuric acid (NUA) Cmax fell within the pre-specified bounds of [0.7, 1.43].Results: The GMRs for NUA Cmax demonstrated similarity in the pharmacokinetics of NER uncoated 2 × 500 mg, NER coated 1 × 1000 mg, and NER coated 2 × 500 mg. Although less stringent comparability bounds were prespecified for the primary pharmacokinetic endpoint (i.e., Cmax of plasma NUA), inspection of the primary comparison of interest indicated that a hypothesis with more stringent bioequivalence bounds of [0.8, 1.25] would have been satisfied. The NUA Cmax for NER uncoated 1 × 1000 mg was approximately 40% higher than that seen for the other three treatments. In contrast, total urinary excretion of niacin and its metabolites, an approximate measure of bioavailability, was similar for all four treatments.Conclusion: The pharmacokinetic profile of the original NER uncoated formulation dosed as 2 × 500 mg was similar to the new film-coated formulation, NER coated, dosed as 1 × 1000 mg.

A Liquid Chromatography−Quadrupole Time-of-Flight (LC−QTOF)-based Metabolomic Approach Reveals New Metabolic Effects of Catechin in Rats Fed High-Fat Diets

Unbalanced diets generate oxidative stress commonly associated with the development of diabetes, atherosclerosis, obesity and cancer. Dietary flavonoids have antioxidant properties and may limit this stress and reduce the risk of these diseases. We used a metabolomic approach to study the influence of catechin, a common flavonoid naturally occurring in various fruits, wine or chocolate, on the metabolic changes induced by hyperlipidemic diets. Male Wistar rats ( n = 8/group) were fed during 6 weeks normolipidemic (5% w/w) or hyperlipidemic (15 and 25%) diets with or without catechin supplementation (0.2% w/w). Urines were collected at days 17 and 38 and analyzed by reverse-phase liquid chromatography-mass spectrometry (LC-QTOF). Hyperlipidic diets led to a significant increase of oxidative stress in liver and aorta, upon which catechin had no effect. Multivariate analyses (PCA and PLS-DA) of the urine fingerprints allowed discrimination of the different diets. Variables were then classified according to their dependence on lipid and catechin intake (ANOVA). Nine variables were identified as catechin metabolites of tissular or microbial origin. Around 1000 variables were significantly affected by the lipid content of the diet, and 76 were fully reversed by catechin supplementation. Four variables showing an increase in urinary excretion in rats fed the high-fat diets were identified as deoxycytidine, nicotinic acid, dihydroxyquinoline and pipecolinic acid. After catechin supplementation, the excretion of nicotinic acid was fully restored to the level found in the rats fed the low-fat diet. The physiological significance of these metabolic changes is discussed.

Effects of hepatic injury or kidney injury on the tryptophan–niacin metabolism in rats

Abstract Hepatic α-amino-β-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis. In normal rats, ACMSD has been generally detectable only in the liver and kidneys. Therefore, there is a possibility that liver or kidney injury affects tryptophan–niacin metabolism. We previously reported the significant change of tryptophan–niacin metabolism in rats with liver cirrhosis or in rats with d -galactosamine injected liver injury. In this experiment, we investigated the change of tryptophan–niacin metabolism in rats treated with puromycin aminonucleoside (PAN)-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan–niacin conversion. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. The reduction of urinary excretion of niacin in nephrotic rats may be due to the reduction of blood tryptophan concentration. The role of the kidney ACMSD may be insignificant concerning tryptophan–niacin conversion under this experimental condition.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidney alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

Fate of nicotinamide differs due to an intake of nicotinamide.

We found that the catabolism of nicotinamide (Nam) differs due to an intake of Nam itself in rats. When rats were fed with a Nam-free, tryptophan-limiting diet, the major catabolite of niacin was N1-methyl-4-pyridone-3-carboxamide (4-Py). However, its percentage was changed with increasing the intake of Nam. The major metabolite was N1-methylnicotinamide (MNA) in the diet containing 0.006% Nam, or 0.1% Nam. The toxicity of excess Nam was observed when rats were fed with a 0.5% Nam-containing diet. In this diet, the major metabolite was Nam N-oxide and it was noted that the urinary excretion of nicotinic acid and its metabolite nicotinuric acid was observed. Therefore, these acids might be detected only when the toxicity of Nam appears.

Relative activity of N-(beta-D-glucopyranosyl)nicotinic acid to nicotinic acid as a niacin nutrient in rats and in Lactobacillus plantarum ATCC 8014.

We investigated the relative activity of N-(beta-D-glucopyranosyl)-nicotinic acid as a niacin nutrient in rats and in Lactobacillus plantarum ATCC 8014. N-(beta-D-Glucopyranosyl)-nicotinic acid is a detoxified product or storage form of nicotinic acid that is found in plants. The relative activity of N-(beta-D-glucopyranosyl)nicotinic acid to nicotinic acid in rats was 1/2.3, 1/2.2, 1/1.0, and 1/1.7 as indices of the body weight gain, food intake, blood NAD content, and the increased urinary excretion of niacin and its metabolites, respectively. N-(beta-D-Glucopyranosyl)nicotinic acid had no niacin activity in Lactobacillus plantarum ATCC 8014.

Tryptophan-Stoffwechseluntersuchungen bei unbehandelten Phenylketonurikern

The products of the oxidative degradation of tryptophan via the kynurenine pathway were quantitatively determined in the urine of ten untreated patients with phenylketonuria, aged 4--35 years. All the patients were sevrely mentally retarded. The results of the analysis suggest a division of the patients into two groups, A and B. The patients of group A showed a basal urinary excretion of kynurenine, kynurenic acid, 3-hydroxykynurenine and xanthurenic acid which lies in the lower part of the normal range. The increase in excretion of tryptophan metabolites under tryptophan loading was, however, significantly less than in controls. On the average, only 0.63 % of the load was excreted in the form of these assayed metabolites; in contrast, the control value is 1,13 %. In group B, the rate of excretion was higher than normal under basal and loading conditions. The post-tryptophan excretion was four times greater than that of controls (4.64 %). 3-hydroxyanthranilic acid could only be detected in group B after loading. The metabolite 8-hydroxyquinaldic acid, which is supposed to be an abnormal metabolic product of tryptophan, was excreted in milligram amounts. The analysis of the metabolites of 3-hydroxyanthranilic acid showed that the excretion of N1-methylnicotinamide and N1-methyl-2-pyridone-5-carboxamide was within the normal range. The excretion of nicotinic acid and its amide was sporadic in both the patients and controls. Other theoretically possible metabolites in the pathway could not be found. A number of unidentified metabolites could be detected by thin-layer chromatography in the basal state. The excretion of these metabolites was greatly augmented after tryptophan loading. Other substances which were not detectable in the basal state became evident on loading. A number of these metabolites are characteristic either of group A or B. The structural identification of one of the new products has been hindered by its instability. A stable cleavage product was identified as omicron-aminoacetophenon by mass-spectroscopy. This metabolite its typical for group B. The possible influence of the blood phenylalanine on the metabolism of tryptophan in phenylketonuria is discussed.

Metabolic relationship between tryptophan, vitamin B6 and nicotinc acid in rats.

Experiments were carried out in regard to the effect of tryptophan and vitamin B6 deficiency on tryptophan and niacin metabolites. Tryptophan-deficient rats promptly lost weight, and the administration of tryptophan to the diet resulted in a rapid gain in weight. Nitrogen loss was found in tryptophan-deficient rats, and nitrogen retention occurred when tryptophan was supplemented to the diet. There was no apparent effect of vitamin B6 supplement on the excretion of nitrogen. The increase of urinary xanthurenic acid by vitamin B6-deficient rats was seen when tryptophan was supplemented.Vitamin B6 had no effect on the excretion of niacin and N1-methylnicotinamide (MNA) and N1-methyl-2-pyridone-5-carboxiamide (pyridone).

Beziehungen zwischen Pflanzen und epiphytischen Bakterien hinsichtlich ihres Auxinstoffwechsels: XII. Die Ausscheidung von Aminosäuren und Vitaminen durch epiphytische Bakterien

Summary This investigation was undertaken in order to detect substances which are, besides IAA excreted by epiphytic bacteria. Two possible ways by which such substances could affect the auxin content of the host plants of the bacteria are regarded: Firstly they could serve as precursors for the IAA production performed by other epiphytic bacteria, secondly they could enter the host plants and interfere with their auxin metabolism. Tryptophan would be an example of the first mode of action, niacin and niacide examples of the second one. Epiphytic bacteria, isolated from pea and corn plants and grown in batch culture, excreted into the culture medium sixteen ninhydrine positive substances, probably amino acids. Mainly living bacteria cells seemed to be able to excrete these substances. Six of nine bacteria strains isolated from corn plants excreted tryptophan, even in the absence of an organic nitrogen source. The rate of tryptophan excretion increased with increasing duration of culturing, the main amount being accumulated during the stationary phase of bacteria growth. Tryptophan was not detectable in a suspension of dead bacteria cells having been killed by autoclaving. The tryptophan produced by living bacteria cells probably contributes to the tryptophan pool existing on the plant surface. Even when cultivated in media without organic nitrogen sources, epiphytic bacteria strains produced niacin. Addition of glutamic acid or tryptophan stimulated niacin production and lead, in one of three strains tested, to niacide production, too. As tryptophan was not more effective than glutamic acid, the former seemed not to be a niacin precursor in these bacteria. There was no correlation between the abilities of the tested epiphytic bacteria strains to produce niacin and niacide and to increase the auxin content of their host plants. Moreover, the produced niacin and niacide amounts were too low for being able to exert an influence on the IAA production in the host plants as demonstrated by the comparison with previous results regarding the effect of niacide applications on the auxin content in the plant. There are also some other experimental reasons for the statement that epiphytic bacteria are able to raise the auxin level of their host plant not by excretion of niacin or niacide, but only by IAA excretion.

Metabolic Patterns in Preadolescent Children: XIV. Excretion of Niacin or Tryptophan Metabolites by Girls Fed Controlled Diets Supplemented with Nicotinamide

A metabolic study was carried out with twelve 7- to 9-year-old girls maintained with 5 controlled diets varying in niacin content from 10 to 31 mg/day. The adjustment diet and two of the four experimental diets were supplemented with crystalline nicotinamide in gelatin capsules. Urinary excretion of N1-methyl-nicotinamide, N1-methyl-2-pyridone-5-carboxamide, niacin, and quinolinic acid were measured during an adjustment period and during 6 consecutive 6-day experimental periods. Subjects fed a low-protein, low-riboflavin diet or a moderate-protein, adequate-riboflavin diet supplemented with 10.3 mg/day of nicotinamide excreted 8.9 and 8.2 mg more of niacin metabolites (NM) per day than did girls fed the same diets without supplemental niacin. The girls fed the low-protein, low-riboflavin diet supplemented with crystalline nicotinamide excreted more NM than predicted from a regression equation. Thus it is possible that the low protein or riboflavin content, or both, of this diet resulted in a lowered requirement for niacin by these subjects or interfered with their utilization of the added nicotinamide. Almost constant excretion of NM was attained after the girls were fed the controlled diets for only 6 days.

Metabolic Patterns in Preadolescent Children: VII. Intake of Niacin and Tryptophan and Excretion of Niacin or Tryptophan Metabolites

Metabolic Patterns in Preadolescent Children: VII. Intake of Niacin and Tryptophan and Excretion of Niacin or Tryptophan Metabolites

Excretion of nicotinic acid and nicotinic acid adenine dinucleotide by biotin-deficient yeast.

Excretion of Nicotinic Acid and Nicotinic Acid Adenine Dinucleotide by Biotin-Deficient Yeast

Nicotinic acid-tryptophan metabolism in certain diseases.

Summary1. Urinary excretions of nicotinic acid and amide, quinilinic acid, N'-methylnicotinamide, 6-pyridone, tryptophan, kynurenin, anthranilic acid and 3-hydroxyanthranilic acid were estimated in normal men and in patients suffering from typhoid fever, cholera, small pox, cirrhosis of liver and infective hepatitis both before and for 3 days after the feeding of tryptophan. 2. Excretion of tryptophan both before and after feeding diminished in all the diseases studied. Kynurenin which was absent initially in the urine of patients appeared in urine collected for 24 hours after the feeding of tryptophan in small pox, liver cirrhosis and hepatitis but not in cholera. 3-hydroxyanthranilic acid appeared in urine after tryptophan was fed in cholera, small pox and hepatitis but not in cirrhosis of liver. In all diseased conditions studied, except in typhoid and small pox, urinary excretion of nicotinic acid and its metabolites was greatly diminished. After administration of tryptophan urinary excretion of nicot...

Effects of Method of Preservation of Roughage, and of Cane or Wood Molasses on Vitamin Excretion by Cows

Summary Three methods of preservation and storage of hay were compared with respect to their effect upon vitamin synthesis in the digestive tract of cows fed the hays. Fecal and urinary excretions of the vitamins were measured. Whether the roughage was field-cured, mow-cured or ensiled had no significant effect upon the excretion of nicotinic acid, pantothenic acid or riboflavin. Silage apparently favorably affected the synthesis of thiamine in the digestive tract. As a feed for dairy cattle, wood molasses was found to be comparable to cane molasses with respect to its effect upon rumen or intestinal synthesis of nicotinic acid, thiamine and pantothenic acid. In the case of pantothenic acid, this synthetic activity was considerably increased when molasses was present.

Effects of Radiation Therapy on the Urinary Excretion of Niacin and Riboflavin in Patients with Malignant Diseases

Concepts concerning the etiology of radiation sickness have been numerous and varied. In 1906, Edsall and Pemberton suggested that the vomiting was toxic in nature and was due to unknown decomposition products of tissue destruction (5). Later, Hall and Whipple (7) attributed the effects to injury of the epithelial cells, and Rolleston (14) felt that proteins liberated by the destruction of cells were responsible for the symptoms. Holmes and Hunter noted that the manifestations closely resembled those seen in patients with catarrhal jaundice, and suggested the possibility of a disturbance of liver function as the underlying cause (8). More recently, there has been much interest in the relationship of vitamins to radiation sickness. Martin and Moursund, in 1938, pointed out that this condition resembled a vitamin B1 deficiency and stated that vitamin B1 protected guinea-pigs from sickness following small doses of radiation over the abdomen (10). In the same year, Spies and his co-workers found that patients...

The Nutrition of the Newborn Dairy Calf. II. Effect of Dietary Tryptophan on the Urinary Excretion of Niacin and its Metabolites by Young Dairy Calves

Summary Five g. of tryptophan were fed daily for 3 days to each of two dairy calves that had been maintained from birth on a whole milk diet. The amount of urinary excretion of nicotinic acid and its derivatives and tryptophan was determined on 24-hour samples and compared with similar data obtained previous to and following the tryptophan feeding. Tryptophan feeding resulted in a three- to four-fold increase in the excretion of total free and combined nicotinic acid. There was little change in the excretion of free nicotinic acid and N 1 -methylnicotinamide. The major portion of the increase was in the non-methylated products. The data indicate that N 1 -methylnicotinamide was not the main metabolic product excreted by calves. The urinary excretion of tryptophan accounted for only 1 to 1.5 per cent of the intake. Increase in dietary tryptophan results in increased urinary excretion of total nicotinic acid, indicating that tryptophan serves as a precursor of niacin in the young calf as in other mammals thus far studied.

EXCRETION OF NICOTINIC ACID IN TYPHOID

THE LITERATURE contains many reports on the association of typhoid and pellagra. Bean and others, 1 in a review on secondary pellagra, assumed that in typhoid the rise in metabolism due to the prolonged fever leads to increased demands on the system of catalysts and brings about a state of deficiency. Sarma 2 in 1943 described the deficiency of nicotinic acid in patients with typhoid. Symptoms of this condition were glossitis and cerebral disturbances such as mania, confusion, delirium and melancholia. These symptoms could be relieved by treatment with nicotinic acid. Deficiency of nicotinic acid following typhoid has been observed in the Hadassah Rothschild University Hospital as well. 3 However, no laboratory investigations on the metabolism of nicotinic acid in typhoid have as yet been reported. The study reported here was undertaken with the purpose of examining the urinary excretion of nicotinic acid in typhoid and of establishing a possible relationship between the rate of excretion of

Excretion of Nicotinic Acid in Pellagra.

The observations reported here indicate that the urinary excretion of nicotinic acid in pellagra is not significantly different from that of the normal.