COMPARING FOLIC ACID PHARM ACOKINETICS AMONG WOMEN OF CHILDBEARING AGE: SINGLE DOSE INGESTION OF 1.1 MG VERSUS 5 MG FOLIC ACID

Patricia Nguyen; Rada Boskovic; Parvaneh Yazdani; Bhushan Kapur; Hilde Vandenberghe; Gideon Koren

Patricia Nguyen

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Canada; The Motherisk Program, The Hospital for Sick Children, Toronto, Canada

Rada Boskovic

The Motherisk Program, The Hospital for Sick Children, Toronto, Canada

Parvaneh Yazdani

The Motherisk Program, The Hospital for Sick Children, Toronto, Canada

Bhushan Kapur

The Motherisk Program, The Hospital for Sick Children, Toronto, Canada; Department of Clinical Pathology, Sunnybrook Health Sciences Center, Toronto, Canada; Department of Pathobiology and Laboratory Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada

Hilde Vandenberghe

Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, Canada

Gideon Koren

Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Canada; The Motherisk Program, The Hospital for Sick Children, Toronto, Canada

Keywords

Folic acid, pharmacokinetics, NTD, pregnancy, multivitamin

Abstract

Background

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.

Objective

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.

Method

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.

Results

The mean area under the curve (AUC) of 1.1 mg and 5 mg folic acid were 147.6 ± 52.8 (ng/mL)?hr and 997.5 ± 271.9 (ng/mL)?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.

Conclusion

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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References

1. Daly LE, Kirke PN, Malloy A, Weir D, Scott JM. Folate Levels and Neural Tube Defects: Implications for Prevention. Journal of the American Medical Association
1995;274(21):1698-1702.
2. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-7.
3. Czeizel AE, Dudas I. Prevention of the first occurrence of neural- tube defects by periconceptional vitamin supplementation. New England Journal of Medicine 1992;327:1832-5.
4. Goh YI, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: A meta-analysis. Journal of Obstetrics and Gynaecology Canada 2006;28:680-9.
5. Goh YI, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis. Clin Pharmacol Ther. 2007;81(5):685-91.
6. Wald NJ, Law MR, Morris JK, Wald DS. Quantifying the effect of folic acid. The Lancet 2001;358: 2069-73.
7. Repchinsky C. (Editor-in-Chief). Compendium of Pharmaceuticals and Specialties (9 Ed.).Ottawa, Canada. Canadian Pharmacists Association. 2007:1843.
8. Repchinsky C. (Editor-in-Chief). Compendium of Pharmaceuticals and Specialties (9th Ed.). Ottawa, Canada. Canadian Pharmacists Association. 2007:1843-4.
9. Nguyen P, Nava-Ocampo A, Levy A, et al. Effect of iron content on the tolerability of prenatal multivitamins in pregnancy. BMC Pregnancy and Childbirth 2008;8:17.
10. Ahn E, Kapur B, Koren G. Study on circadian variation in folate pharmacokinetics. Canadian Journal of Clinical Pharmacology 2005;12(1):e4- 9.
11. Dawson EB, Evans DR, Conway ME, McGanity WJ. Vitamin B12 and folate bioavailability from two prenatal multivitamin/multimineral supplements. Am J Perinatol 2000;17:193-99.
12. Institute of Medicine. Food and Nutrition Board. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press;1998.
13. Schaefer RM, Teschner M, Kosch M. Folate metabolism in renal failure. Nephrology, Dialysis, Transplantation 2002;17[Suppl 5]:24-27.
14. Fuller NJ, Bates CJ, Evans PH . High folate intakes related to zinc status in preterm infants. Eur J Pediatr 1992;151:51-53.
15. Cuskelly GJ, Mooney KM, Young IS. Folate and Vitamin B12: friendly or enemy nutrients for the elderly. Proceedings of the Nutrition Society 2007;66:548-558.
16. Herbert V. The 1986 Herman Award Lecture. Nutrition science as a continually unfolding story: the folate and vitamin B12 paradigm. American Journal of Clinical Nutrition 1987;46:387- 402.
17. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probably benefits of increasing folic acid intakes. JAMA 1995;274:1049 -57.
18. Schorah CJ, Devitt H, Lucock M, Dowell AC. The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study. European Journal of Clinical Nutrition 1998;52:407 -411.
19. Holmes V, Wallace J, Alexander H, et al. Homocysteine is lower in the third trimester of pregnancy in women with enhanced folate status from continued folic acid supplementation. Clinical Chemistry 2005;51(3):629-634.
20. Bar-Oz B, Koren G, Nguyen P, Kapur B. Folate fortification and supplementation – Are we there yet? Reproductive Toxicology 2008;25:408-412.
21. Koury MJ, Ponka P. New Insight into Erythropoiesis: The roles of folate, vitamin B12, and iron. Annual Review of Nutrition 2004;24:105-31.
22. Ray JG, Wyatt PR, Thompson MD, et al. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology 2007;18(3):362-6.
23. Wilson RD, Johnson JA, Wyatt P, et al. Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada and The Mother isk Program. Pre- conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. Journal of Obstetrics and Gynecology Canada 2007;29(12):1003-26.
24. Centers for Disease Control and Prevention. Department of Health and Human Services (2005)Folic Acid. Accessed on January 7, 2007. http://www.cdc.gov/ncbddd/folicacid/faqs.htm# women
25. World Health Organization. Department of Making Pregnancy Safer. (2006). Prevention of neural tube defects. Accessed on January 7, 2007. http://www.who.int/making_pregnancy_safer/pu blications/en/

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Published

Dec 8, 2018

How to Cite

Nguyen, P., Boskovic, R., Yazdani, P., Kapur, B., Vandenberghe, H., & Koren, G. (2018). COMPARING FOLIC ACID PHARM ACOKINETICS AMONG WOMEN OF CHILDBEARING AGE: SINGLE DOSE INGESTION OF 1.1 MG VERSUS 5 MG FOLIC ACID. Journal of Population Therapeutics and Clinical Pharmacology, 15(2). Retrieved from https://jptcp.com/index.php/jptcp/article/view/211