Pharmacokinetic Profile of Flavin Adenine Dinucleotide, Flavin Mononucleotide and Riboflavin Following Intravenous Administration of Riboflavin or Its Coenzymes in Rats

Abstract

The pharmacokinetics and utilization (flavocoenzyme formation) of an intravenously administered flavin mononucleotide (FMN) or riboflavin (RF) in rats were assessed using ethylenediamine-N, N, N , N -tetraacetic acid (EDTA)-treated plasma. Serial blood samples were collected via a syringe containing EDTA, used to prevent flavin adenin dinucleotide (FAD) hydrolysis, from the left jugular vein and plasma samples were analyzed for FAD, FMN and RF levels using a reversed-phase HPLC method. After the intravenous bolus administration of a single dose of FMN (500 nmol/kg), FAD was identified in plasma. However, increased levels of FAD in plasma were much less pronounced than that of RF levels. In contrast, after the intravenous bolus administration of single dose of RF (500 nmol/kg), both FAD and FMN levels were not different from the endogenous levels. Evidence is given in this paper that intravenously administered FMN affects the plasma levels of FAD in rats, whereas insensible changes in FMN and FAD levels were not confirmed by intravenously administered RF. The plasma kinetics of total flavin after intravenous bolus administration of RF, FMN or FAD to rats was also estimated. Statistical analysis of individual data revealed a high correlation between the total flavin level obtained by summation of each flavin level and that obtained with the lumiflavin (LF) method. Since this method is highly sensitive, it could * To whom correspondence should be addressed: Faculty of Pharmaceutical Science, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan. Tel.:+81-475-53-4524; Fax: +81-475-53-4521; E-mail: makimoto@jiu.ac.jp be used to give precise values for the pharmacokinetic parameters of flavins.