1. Kinetic profile of overall elimination of 5-methyltetrahydropteroylglutamate in rats.
- Author
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Han YH, Kato Y, Kusuhara H, Suzuki H, Shimoda M, Kokue E, and Sugiyama Y
- Subjects
- Animals, Bile metabolism, Folic Acid blood, Folic Acid metabolism, Homeostasis physiology, Kidney metabolism, Liver metabolism, Male, Rats, Rats, Sprague-Dawley, Tetrahydrofolates urine, Tetrahydrofolates pharmacokinetics
- Abstract
The in vivo biliary and urinary excretion kinetics of 5-methyltetrahydropteroylglutamate (5-CH3-H4PteGlu) were studied in rats. During infusion at various rates (48-965 nmol. h-1. kg-1), the total body clearance (CLtotal) of 5-CH3-H4PteGlu could be attributed almost entirely to the sum of the biliary and urinary (CLurine,p) excretion clearances. After a 4-h infusion at the highest rate, the 5-CH3-H4PteGlu in the liver was 10 times higher than the endogenous level, whereas its polyglutamate form did not increase, suggesting that most of the infused 5-CH3-H4PteGlu is not incorporated in the polyglutamate pool but is eliminated by excretion. The parallel increase in CLtotal and CLurine,p with the increase in infusion rate might result from saturation of reabsorption at the renal proximal tubules, since the urinary excretion clearance, defined with respect to the kidney concentration, also increased while the biliary excretion clearance, defined with respect to the liver concentration, remained almost constant. We conclude that the hepatobiliary excretion is a relatively low-affinity process with a constant clearance, whereas the renal tubular reabsorption is saturated at higher plasma 5-CH3-H4PteGlu concentration ( approximately 0.5 microM). Urinary excretion becomes the predominant elimination route for any excess 5-CH3-H4PteGlu in the body.
- Published
- 1999
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