Pharmacokinetic comparison of leucovorin and levoleucovorin

Abstract

The pharmacokinetic values of d,l-leucovorin and l-leucovorin were compared in eight healthy volunteers following oral administration of 25 mg d,l-leucovorin and 12.5 mg l-leucovorin. Serum levels of l-5-formyltetrahydrofolate, l-5-methyltetrahydrofolate, and total reduced folates were measured by an established microbiological method. Pharmacokinetic data for both preparations were consistent with those previously reported for d,l-leucovorin, with essentially complete first pass metabolism to l-5-methyltetrahydrofolate, the active metabolite. No differences were found between the two preparations in serum concentrations of active folate fractions, AUC, or Cmax, or in clearance and volume of distribution estimates. These data suggest that after administration of 25 mg of d,l-leucovorin, the d-diastereoisomer has no significant effect on the standard pharmacokinetic measurements of the active l-folates.

Structure of 5-formyltetrahydrofolate cyclo-ligase fromBacillus anthracis(BA4489)

“…Folate metabolism and the role of 5-formyl-THF cyclo-ligase. (a) An overview of bacterial folate metabolism (modified from Zittoun & Zittoun, 1972). Both folate and the one-carbon group it carries can exist in different oxidation states, which are interconvertable.…”

Effect of freeze-thawing on the long-term stability of calcium levofolinate in 5% dextrose stored on polyolefin infusion bags

“…The bags were then stored at 5 ± 3°C for 1 month. Immediately after the preparation of the bags and after thawing (day 0) 2 mL of solution were withdrawn for assay at 0, 1,2,4,7,9,11,14,16,18,22,28 and 30 day after storage at 5 ± 3°C, from each of the five bags by means of a 2 mL single-use sterile syringe with needle (Terumo, Leuven, Belgium) and were placed in a glass container. The admixtures were visually inspected (colour, appearance, precipitation) through the bags prior to sampling and the pH of the samples were measured.…”

“…Levofolinic acid, the L-diastereoisomer of the 5-formyl derivative of tetrahydrofolic acid, is the naturally occurring active form of the drug. The use of the active enantiomer reduces to half the doses administered to the patient and avoid the body to eliminate the non-active drug (1,2). Calcium levofolinate has the same indication as folinic acid salts.…”

Stability of calcium levofolinate, 5-fluorouracil and oxaliplatin (FOLFOX) mixture

“…Given that high intracellular levels of 5,10-methylene tetrahydrofolate are necessary for optimal binding of 5-fluoro-2'-deoxyuridine 5'-monophosphate to thymidylate synthase, LV has been used for this purpose and the coupling of 5-FU/LV has shown to generate superior response rates as compared with 5-FU, although this combination did not result in improved overall survival. 2 Oxa (Figure 1(c)) or oxalato(trans-L-1,2-diaminocyclohexane)platinum, a platinum-based drug, presents various mechanisms of action. Mostly, after non-enzymatic transformation in plasma, reactive compounds form cross-linking adducts thereby blocking DNA replication and transcription.…”