Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans

Abstract

The pharmacokinetics and utilization (flavocoenzyme synthesis) of orally and intravenously administered riboflavin in healthy humans were assessed. After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females (control period), each of these subjects received three different oral riboflavin doses (20, 40, and 60 mg) and one intravenous bolus injection of riboflavin (11.6 mg). Vitamins were administered in a randomized, cross-over design with 2 wk between each administration. Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration. Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma; riboflavin was assayed in urine. During the control period, a small circadian variation was observed: plasma concentrations and urinary excretion of riboflavin were low during the afternoon (P < 0.05). Pharmacokinetics were calculated using a two-compartment open model. The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult. Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration (P < 0.01). Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations. 7 alpha-Hydroxyriboflavin was identified in plasma. Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma. No sex differences were observed for any of the pharmacokinetic variables (P > 0.05).

Conversion of FAD to FMN and Riboflavin in Plasma: Effects of Measuring Method

“…the coenzyme forms of vitamin B 2 were analyzed in total as FMN. The apparent discrepancies between our sample processing and that published by Zempleni et al 4) can be attributed in part to different temperature conditions and anticoagulants. Notably, we used a large excess of EDTA, which showed to inhibit the enzymatic activity that hydrolyzes FAD and FMN.…”

“…Because of a rapid hydrolysis of FAD in plasma after sample collection, the coenzyme forms of VB 2 were determined in total as FMN by acid hydrolysis. [4][5][6] Therefore, simultaneous determinations of RF, FMN and FAD in plasma have not widely used for pharmacokinetic studies of orally and intravenously administered VB 2 in animals and humans.…”

Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1

“…In addition, the subject of riboflavin excretion has gained increasing attention. Jusko et al (18,19) and others (7,25,40,45) demonstrated saturable renal reabsorption and accumulation of riboflavin. Therefore, riboflavin transporters are thought to be essential for the maintenance of riboflavin homeostasis in the intestine and kidney.…”

Urinary Water-Soluble Vitamins as Nutritional Biomarker to Estimate Their Intakes

“…Urinary excretion of water-soluble vitamins such as thiamin, riboflavin and niacin has been used for setting Dietary Reference Intakes (DRIs) in USA and Japan (Food and Nutrition Board, Institute of Medicie, 1998; The Ministry of Health, Labour, and Welfare, 2009). Although pharmacological dose of watersoluble vitamin intake such as vitamin B 2 (Zempleni et al, 1996), nicotinamide (Shibata & Matsuo, 1990) and biotin (Zempleni & Mock, 1999) dramatically increase urinary vitamin levels, a few study had studied about the relationship between several oral dose correspond to dietary intake and urinary excretion of vitamin C (Levine et al, 1996(Levine et al, , 2001). Thus, little attention had been paid to assess the quantitative relationships between intakes and urinary excretion of water-soluble vitamins.…”