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Can J Clin Pharmacol. 2008 Summer;15(2):e314-22. Epub 2008 Aug 18.

Comparing folic acid pharmacokinetics among women of childbearing age: single dose ingestion of 1.1 versus 5 MG folic acid.

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Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Canada.



A 2001 study suggested that supplementation with 5 mg folic acid, among women of childbearing age, is needed to render maximum protection against neural tube defects (NTD). No human study is presently available which examined the pharmacokinetics of 5 mg folic acid.


To compare the pharmacokinetics of ingesting a single dose of 5 mg versus 1.1 mg folic acid contained in 2 prenatal multivitamins (PregVit and PregVit-Folic 5), and to estimate its contribution to steady-state folate levels.


The pharmacokinetics of 1.1 mg folic acid was determined in a previously published study. The method was replicated among 6 healthy, non-pregnant women who were given 5 mg folic acid to ingest. Blood samples were drawn and serum folate concentrations were measured at various time points during 10 hours post-ingestion. Standard pharmacokinetic parameters were determined and compared with Student's t-test, when appropriate.


The mean area under the curve (AUC) of 1.1 mg and 5 mg folic acid were 147.6 +/- 52.8 (ng/mL) x hr and 997.5 +/- 271.9 (ng/mL) x hr, respectively (p<0.0002). An approximate 5-fold difference was detected in the peak concentrations (Cmax) between the 2 groups (p<0.0005), alongside a slight difference in the times to peak (Tmax) (p=0.02). The estimated steady-state serum folate concentrations produced by 1.1 mg and 5 mg folic acid were 6.2 +/- 2.2 ng/mL and 41.6 +/- 11.3 ng/mL, respectively (p<0.0002), prior to its summation with initial (baseline) steady-state levels.


Single dose administration between 1.1 mg and 5 mg folic acid demonstrated linear pharmacokinetics, with approximately a 5-fold difference between the 2 doses in serum folate contribution to steady-state levels, under ideal adherence.

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