Vol. 276, Issue 3, E580-E587, March 1999
Kinetic profile of overall elimination of
5-methyltetrahydropteroylglutamate in rats
Yong-Hae
Han1,
Yukio
Kato1,
Hiroyuki
Kusuhara1,
Hiroshi
Suzuki1,
Minoru
Shimoda2,
Eiichi
Kokue2, and
Yuichi
Sugiyama1
1 Graduate School of
Pharmaceutical Sciences, University of Tokyo, Hongo, Tokyo 113-0033;
and 2 Faculty of
Agriculture, Tokyo University of Agriculture and Technology, Fuchu,
Tokyo 183-005, Japan
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 · kg1),
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 (~0.5 µM). Urinary excretion becomes the predominant
elimination route for any excess
5-CH3-H4PteGlu in the body.
folate; biliary excretion; urinary excretion; homeostasis
