Red blood cell partitioning of the [6S]- and the [6R]-isomer of N5-formyltetrahydrofolic acid.
The in vitro interaction of the [6S]- and [6R]-stereoisomers of CHO-THFA with human RBCs was investigated in the (therapeutically comparable) concentration range from 1.0 to 12.5 micrograms/ml. Both compounds are bound to RBCs with a kRBC ranging from 0.13 to 0.75 for [6S]-CHO-THFA and from 0.06 to 0.33 for [6R]-CHO-THFA, respectively. The interaction of the [6S]-form with RBCs is about two times higher than of the [6R]-form. Incubation of CHO-THFA with RBCs over 24 h showed an accelerated disappearance from the test solution for [6R]-CHO-THFA with a mean t1/2 of 49.9 h in compare to t1/2 = 58.2 h for the [6S]-enantiomer. The results indicate that RBCs may play a major role for the pharmacokinetics and metabolism of CHO-THFA and may act as an intravasal depot especially for [6S]-CHO-THFA.
Czejka
M J
MJ
Institute for Pharmaceutical Chemistry, University of Vienna, Austria.
Schüller
J
J
Scheithauer
W
W
D001665:Binding Sites; D004912:Erythrocytes / Q000378:metabolism*; D005575:Formyltetrahydrofolates / Q000097:blood*; D006801:Humans; D007700:Kinetics; D013237:Stereoisomerism
D005575:Formyltetrahydrofolates