Involvement of organic cation transporters in the clearance and milk secretion of thiamine in mice

Pharm Res. 2015 Jul;32(7):2192-204. doi: 10.1007/s11095-014-1608-8. Epub 2015 Feb 21.


Purpose: To investigate the role of organic cation transporters (Octs) and multidrug and toxin extrusion protein 1 (Mate1) in the disposition of thiamine.

Methods: The uptake of [(3)H]thiamine was determined in Oct1-, Oct2-, and Oct3-expressing HEK293 cells and freshly isolated hepatocytes. A pharmacokinetic study of thiamine-d3 following intravenous infusion (1 and 100 nmol/min/kg) was conducted in male Oct1/2(+/+) and Oct1/2(-/-) mice. A MATE inhibitor, pyrimethamine, (5 mg/kg) was administered intravenously. The plasma and breast milk concentrations of thiamine were determined in female mice.

Results: Thiamine is a substrate of Oct1 and Oct2, but not Oct3. Oct1/2 defect caused a significant reduction in the uptake of [(3)H]thiamine by hepatocytes in vitro, and elevated the plasma thiamine concentration by 5.8-fold in vivo. The plasma clearance of thiamine-d3 was significantly decreased in Oct1/2(-/-) mice. At the higher infusion rate of 100 nmol/min/kg thiamine-d3, Oct1/2 defect or pyrimethamine-treatment caused a significant reduction in the renal clearance of thiamine-d3. The total thiamine and thiamine-d3 concentrations were moderately reduced in the intestine of Oct1/2(-/-) mice but were unchanged in the kidney, liver, or brain. The milk-to-plasma concentration ratio of thiamine was decreased by 28-fold in the Oct1/2(-/-) mice.

Conclusions: Oct1 is possibly responsible for the plasma clearance of thiamine via tissue uptake and for milk secretion. Oct1/2 and Mate1 are involved in the renal tubular secretion of thiamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Catecholamine Plasma Membrane Transport Proteins / genetics
  • Catecholamine Plasma Membrane Transport Proteins / metabolism*
  • Chromatography, Liquid
  • HEK293 Cells
  • Hepatocytes / metabolism*
  • Humans
  • Lactation
  • Male
  • Metabolic Clearance Rate
  • Mice, Knockout
  • Milk / metabolism*
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism*
  • Tandem Mass Spectrometry
  • Thiamine / blood
  • Thiamine / metabolism
  • Thiamine / pharmacokinetics*
  • Tissue Distribution
  • Transfection


  • Catecholamine Plasma Membrane Transport Proteins
  • MATE1 protein, mouse
  • Organic Cation Transport Proteins
  • Slc22a1 protein, mouse
  • Thiamine