Pharmacokinetic comparison of leucovorin and levoleucovorin

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Metabolism

Background:

• Leucovorin is a crucial folate analog used in various medical treatments.
• Understanding the pharmacokinetics of different leucovorin forms is essential for optimizing therapeutic use.
• d,l-Leucovorin contains both active (l-form) and inactive (d-form) diastereoisomers.

Purpose of the Study:

• To compare the pharmacokinetics of d,l-leucovorin and l-leucovorin after oral administration.
• To determine if the d-diastereoisomer of leucovorin affects the pharmacokinetic profile of the active l-folate metabolites.

Main Methods:

• Eight healthy volunteers received oral doses of 25 mg d,l-leucovorin or 12.5 mg l-leucovorin.
• Serum concentrations of l-5-formyltetrahydrofolate, l-5-methyltetrahydrofolate, and total reduced folates were measured.
• Standard pharmacokinetic parameters including AUC, Cmax, clearance, and volume of distribution were analyzed.

Main Results:

• Pharmacokinetic data for both preparations were consistent with prior d,l-leucovorin studies.
• First-pass metabolism led to the active metabolite, l-5-methyltetrahydrofolate.
• No significant differences were observed in serum concentrations of active folate fractions, AUC, Cmax, clearance, or volume of distribution between the two preparations.

Conclusions:

• Oral administration of 25 mg d,l-leucovorin results in pharmacokinetic parameters comparable to l-leucovorin alone.
• The d-diastereoisomer in d,l-leucovorin does not appear to influence the pharmacokinetics of the active l-folate metabolites.
• These findings support the use of d,l-leucovorin with comparable efficacy to l-leucovorin regarding folate absorption and metabolism.