a rise in serum unconjugated bilirubin in normal individuals and in those with Gilbert's Syndrome. However, in the Gilbert's Syndrome, the rise in bilirubin is higher and clearance is delayed longer than in normal people. One test used to aid in diagnosing Gilbert's Syndrome involves intravenous administration of nicotinic acid (niacin) in a dose of 50 mg over a period of 30 seconds. Pharmacokinetics Both niacin and niacinamide are rapidly absorbed from the stomach and small intestine. Absorption is facilitated by sodium-dependent diffusion, and at higher intakes, via passive diffusion. Unlike some other vitamins, the percent absorbed does not decrease with increasing dose, so that even at amounts of 3-4 grams, absorption is nearly complete. With a one gram dose, peak plasma concentrations of 15 to 30 μg/mL are reached within 30 to 60 minutes. Approximately 88% of an oral pharmacologic dose is eliminated by the kidneys as unchanged niacin or nicotinuric acid, its primary metabolite. The plasma elimination half-life of niacin ranges from 20 to 45 minutes. Niacin and nicotinamide are both converted into the coenzyme NAD. NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency. In the liver, niacinamide is converted to storage nicotinamide adenine dinucleotide (NAD). As needed, liver NAD is hydrolyzed to niacinamide and niacin for transport to tissues, there reconverted to NAD to serve as an enzyme cofactor. Excess niacin is methylated in the liver to N1-methylnicotinamide (NMN) and excreted in urine as such or as the oxidized metabolite N1-methyl-2-pyridone-5-carboxamide (2-pyridone). Decreased urinary content of these metabolites is a measure of niacin deficiency. Production Biosynthesis In addition to absorbing niacin from diet, niacin can be synthesized from the essential amino acid tryptophan, a five-step process with the penultimate compound being quinolinic acid (see figure). Some bacteria and plants utilize aspartic acid in a pathway that also goes to quinolinic acid. For humans, the efficiency of conversion is estimated as requiring 60mg of tryptophan to make 1mg of niacin. Riboflavin, vitamin B6 and iron are required for the process. Pellagra is a consequence of a corn-dominant diet because the niacin in corn is poorly bioavailable and corn proteins are low in tryptophan compared to wheat and rice proteins. Industrial synthesis Nicotinic acid was first synthesized in 1867 by oxidative degradation of nicotine.