Red Blood Cell Partitioning of the [6 <S|- and the [6/?]-Isomer of N5-Formyltetrahydrofolic Acid

The in vitro interaction of the [65]and [6Ä]-stereoisomers of CHO-THFA with human RBCs was investigated in the (therapeutically comparable) concentration range from 1.0 to 12.5 ng/ml. Both compounds are bound to RBCs with a kRBC ranging from 0.13 to 0.75 for [65]-CHO-THFA and from 0.06 to 0.33 for [6/?]-CHO-THFA, respectively. The interaction of the [65]-form with RBCs is about two times higher than of the [6i?]-form. Incubation of CHO-THFA with RBCs over 24 h showed an accelerated disappearance from the test solution for [6i?]-CHO-THFA with a mean tv2 o f 49.9 h in compare to t]/2 = 58.2 h for the [65]-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 [65]-CHOTHFA.