Entero-hepatic cycling of methotrexate estimated by use of the D-isomer as a reference marker.
The absorption and elimination kinetics of 4-amino-N10-methylpteroyl-D-glutamic acid (D-MTX), the optical isomer of methotrexate (L-MTX), were examined. Test doses of 10 mg D-MTX were administered i.v. and orally to nine patients and its plasma concentration and urinary excretion were followed. The plasma curves after an i.v. bolus injection of D-MTX declined strictly biexponentially and reached zero after about 16 h. The elimination rate constants were estimated as the terminal first order rate constants. The absorption of orally administered D-MTX, estimated by its 24 h urinary recovery, in all cases was less than 3% of the dose administered. The insignificant intestinal absorption made it possible to estimate the renal and biliary secretion rates of D-MTX from the overall elimination rate constant and from the fraction of the dose excreted in urine. In three of the patients, elimination rate constants both for D-MTX and L-MTX were obtained. The renal elimination rates of the two compounds were found to be nearly identical. The median ratio of biliary/renal excretion of D-MTX was 0.94 (range 0.41-1.50), which indicates extensive entero-hepatic cycling and active absorption of L-MTX at the therapeutic dose levels used in psoriasis.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D004764:Enterohepatic Circulation; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008727:Methotrexate / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine; D008875:Middle Aged; D008954:Models, Biological; D011565:Psoriasis / Q000188:drug therapy; D013237:Stereoisomerism
D008727:Methotrexate