d-leucovorin

d-leucovorin is the (6R)-diastereoisomer of leucovorin (folinic acid), a reduced folate derivative. While leucovorin is typically administered as a racemic mixture of d- and l-isomers, only the l-isomer (levoleucovorin) is biologically active in the metabolic pathways that potentiate 5-fluorouracil or provide a source of reduced folates during methotrexate rescue. d-leucovorin is considered biologically inactive in these therapeutic contexts but is characterized by a significantly longer plasma half-life (approximately 7-9 hours compared to 30-60 minutes for the l-isomer). It competes with l-leucovorin for transport into cells via the reduced folate carrier (RFC1) and for renal clearance, which may lead to competitive inhibition of the active isomer's efficacy. Consequently, pure l-leucovorin formulations have been developed to avoid the potential interference caused by the d-isomer.

Other names

dextroleucovorin(6R)-leucovorin(6R)-5-formyltetrahydrofolate(6R)-folinic acid