Urine niacin

Pharmacokinetics Niacin is rapidly absorbed from the Gl tract peak serum concentrations usually occur within 45 minutes. The plasma elimination half-life is approximately 45 minutes. Approximately one third of an oral dose is excreted unchanged in the urine. 

Drug-induced niacin deficiency has resulted from the use of isonicotinic acid hydrazide, which interferes with the conversion of niacin from tryptophan. Administration of ethanol or the antimetabolites 6-mercaptop-urine and 5-fluorouracil also may lead to niacin deficiency. The uricosuric effects of sulfinpyrazone and probenecid may be inhibited by nicotinic acid. 

Niacin (vitamin B3) is converted in the body to the amide, which is incorporated into niacinamide adenine dinucleotide (NAD). It is excreted in the urine unmodified and as several metabolites. 

Nicotine forms a number of metabolites in the body, mainly in the liver. Approximate 75% of nicotine is oxidized to cotinine, which is the primary nicotine metabolite. Cotinine can be measured in the blood, urine, and saliva and this is used as a measure of nicotine exposure in tobacco users and in those exposed to secondhand smoke. The oxidation of nicotine also produces nicotinic acid. Nicotinic acid is vitamin B3 and has the common name niacin. Niacin deficiency results in a disease called pellagra, which is found in certain malnourished populations. Pellagras symptoms include dermatitis, diarrhea, sensitivity to light, and dementia. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Pharmacokinetics Niacin is administered orally. It is converted in the body to nicotinamide, which is incorporated into the cofactor nicotinamide adenine dinucleotide (NAD+). Niacin, its nicotinamide derivative and other metabolites are excreted in the urine. [Note Nicotinamide alone does not decrease plasma lipid levels.]... 

Acipimox is excreted primarily in the urine as unchanged drug [19]. Sixty to 76% of a dose of niacin is excreted as unchanged drug and metabolites in the urine [1]. 

As acipimox and niacin are not highly protein bound and are not lipophilic, cholestasis should not affect their disposition. They are largely excreted in the urine. Neither has been reported to cause cholestasis. Both may cause pruritus, from which this patient suffers. 

That nongrowing animals require niacin implies that it is lost from the body either as intact niacin or as a modified or breakdown product of the vitamin. An amount of niacin equivalent to nearly 90% of our daily intake is excreted in the forms of N-methyl-2-p)nidone-5urinary metabolites can be used to assess niacin status. Loss of the normal quantity in the urine each day indicates that the supply in the diet is adequate. In humans, the healthy adult excretes 4 to 6 mg of N-methyl-nicoti-namide per day. An abnormally low level indicates that the dietary intake is not adequate. Measurement of urinary niacin metabolites has proven useful in determining the amoimt of niacin available in a variety of foods. The body s ability to use niacin in different foods may vary even if the foods contain identical quantities of the vitamin. One contributing factor to the low availability of niacin is the occurrence of the vitamin in the "bound form," as mentioned earlier. Excretion of normal levels of pyridone, for example, depends not only on normal absorption of the vitamin from the diet, but also on its conversion to NAD or NADP, followed by catabolism to the metabolite. 

Niacin is readily absorbed from the gastrointestinal tract. The peak serum concentration for an immediate release oral dosage form is usually seen within 45 min of niacin ingestion 4-5 h for an extended release tablet. Niacin is hepatically metabolized and widely distributed into body tissues. Niacin is renally excreted. Excess amounts of niacin, beyond daily needs, are excreted largely unchanged in the urine. The plasma half-life is 45 min. 

At present, no blood markers are commonly used as indicators of niacin status. Most assessments of niacin nutriture have been based on measurement of the 2 urinary metabolites, N -methylnicotinamide and N -methyl-2-pyridone-5-carboxamide. Normally, adults excrete 20% to 30% of their niacin in the form of methylnicotinamide and 40% to 60% as the pyridone. An excretion ratio of pyridone to methylnicotinamide of 1.3 to 4.0 is thus normal, but latent niacin deficiency is indicated by a value below 1.0. As depletion occurs, the pyridone is absent for weeks before clinical signs are noted, and the methylnicotinamide excretion falls to a minimum at about the time that clinical signs are evident.f HPLC methods are currently the methods of choice, though some capillary electrophoresis methods have been developed. However, the measurement of 2-pyridone and N -methylnicotinamide concentrations in plasma may provide a more reliable metabolite ratio than urine measurements. A newer approach that may prove valuable is the ratio of NAD/NADP in erythrocytes and plasma tryptophan. A ratio of NAD/NADP below 1.0 would be indicative of a risk of developing niacin deficiency. ... 

Sandhu JS, Fraser DR. Measurement of niacin metabolites in urine by high pressure liquid chromatography. A simple, sensitive assay of niacin nutritional status. Int J Vitam Nutr Res 1981 51 139-44. 

The doses of regular (crystalline) niacin used to treat dyslipidemia are almost completely absorbed, and peak plasma concentrations are achieved within 30-60 minutes. The t is 60 minutes, which accounts for the necessity of twice- or thrice-daily dosing. At lower doses, most niacin is taken up by the liver only the major metabolite, nicotinuric acid, is found in the urine. 

If the dietary levels of niacin and tryptophan are insufficient, the condition known as pellagra results. The symptoms of pellagra are dermatitis, diarrhea, dementia, and, finally, death. In addition, abnormal metabolism of tryptophan occurs in a vitamin B6 deficiency. Kynurenine intermediates in tryptophan degradation cannot be cleaved because kynureninase requires PLP derived from vitamin B6. Consequently, these intermediates enter a minor pathway for tryptophan metabolism that produces xanthurenic acid, which is excreted in the urine. 

The microbiological method using Lactobacillus phntarum, originally described by Snell and Wright (49), has been widely used for the determination of niacin in urine, serum, blood, foods, and tissues (16, 48,50,51,52). This organism is able to detect minute amounts of niacin (1-30 ng/mL) using a turbidimetric or titrimetric assay. 

Fic. 1. Metabolism of tryptophan to serotonin (5-hydroxytryptamine) and niacin. Fyiidoxal phosphate (PLP) dependent reactions are indicated. Reactions not shown which may result in formation of products excreted in urine include the acetylation of liymuenine and 3-hydroxykynurenine, conjugation of anthranilic acid with glycine (to form o-aminohippuric acid) and with glucuronic acid, and the dehydroxylation of kynurenic acid and xanthurenic add to quinaldic add and 8-hydroxyquinaldic add, respectively. 

The work of Haenel et al. (1959), which has been mentioned several times, showed that rats given diets with 20% sorbitol excreted more thiamine, riboflavin, pyridoxine, and niacin in the urine. This confirms that sorbitol can increase the supply of all these substances to the animal. 

Nicotinic acid and nicotinamide These are sometimes known by the generic term niacin. Their importance is in combination with tryptophan, as the coenzyme forms nicotinamide adenine dinucleotide (NAD + ) and nicotinamide adenine dinucleotide phosphate (NADP). HPLC is too insensitive to measure endogenous plasma levels, but the urinary metabolites N-methyl-2-pyridone-5-carboxylamide and N -methylnicotinamide can be measured to assess niacin status. Preliminary cleanup of urine by anion-exchange resins is followed by reversed-phase HPLC with UV detection. 

Vitamins are a chemically and functionally inhomogeneous group of biomolecules. As a gross classification distinction is usually made between (1) fat-soluble and (2) water-soluble vitamins. Owing to their insolubility in water the fat-soluble vitamins A, D, E, and K can be accumulated in fat tissue and excessive intake causes hypervitaminoses. The water-soluble vitamins - vitamin Bj, vitamin B2, niacin, vitamin Bg, folic acid, pantothenic acid, biotin, vitamin B12, and ascorbic acid - can generally only be stored in a small amount and intake exceeding actual need is excreted in the urine. 

Trigonellln 1-methylnicotinic acid, a metabolite of nicotinic acid or nicotinamide found in many plants. It is both a hormone and a storage form of nicotinic acid. It is apparently not a niacin metabolite in animals, although it is found in the urine of coffee drinkers. Green coffee beans contain relatively large (> 500 mg/kg) amounts of X roasting the beans converts T. to nicotinic acid. Coffee is a significant dietary source of niacin (see Vitamins) in South and Central America. 

The absorption of niacin in the human body mainly occurs in the stomach and small intestine (Bechgaard and Jespersen 1977). Niacin is taken up by the body swiftly and quickly, and reaches peak plasma levels within 30-60 minutes of being absorbed (Bodor and Offermanns 2008). Furthermore it has a plasma half-life of 60 minutes (Carlson et al. 1968 Svedmyr and Harthon 1970). The enzyme nicotinamide adenine dinucleotide (NAD) glycohydrolase, which is found in the intestine and liver, faciUtates the synthesis of nicotinamide from NAD (Henderson and Gross 1979). This is an important step that ensures the availability of nicotinamide for the conversion to NAD. Niacin is metabolized in most tissues in the body and its metaboKtes are excreted in urine (Jacob et al. 1989 Shibata and Matsuo 1989). Importantly, niadn deficiency occurs mainly as a result of poor diet, but also other conditions such as carcinoid syndrome, Hartnup s disease and drug intake (isoniazid) (Hegyi et al. 2004). 

Mittal, M.K., Florin, T., Perrone, J., Delgado, J.H., and Osterhoudt, K.C., 2007a. Toxicity from the use of niacin to beat urine drug screening. Annals of Emergency Medicine. 50 587-590. 

Quinolinic Acid. Assignment of a place to quinolinic acid as an intermediate in nicotinic acid formation is based on the evidence that its excretion into the urine is increased by injection of tryptophan or of 3-hydroxyanthranilic acid. Quinolinic acid isolated from the urine on treatment with acid gives rise to a substance having niacin activity for L. arabinosus. ... 

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