STUDY ON CIRCADIAN VARIATION IN FOLATE PHARMACOKINETICS
Main Article Content
Keywords
Folate, bioavailability, circadian rhythm, PregVit®, multivitamins, prenatal
Abstract
Background
In a new preparation of prenatal multivitamins, PregVit®, two tablets a day (a.m. and p.m.) are given. Folic acid is separated from iron and zinc and is given in the p.m. tablet to overcome problems due to folic acid interactions with iron or zinc, and frequent presence of nausea and vomiting of pregnancy in the morning. The circadian variation of folate in humans has not been investigated. This is the first study attempting to determine whether circadian variation of folate pharmacokinetics exists in humans.
Objectives
To determine whether circadian rhythm of folate pharmacokinetics exists in humans.
Methods
In a crossover design, six healthy, non-pregnant women were randomized to receive 1 tablet of PregVit® p.m., containing 1.1 mg of folic acid, in the morning or evening. Serum folate levels were measured over 10 hours. The area under the concentration-time curve (AUC) was used to compare the extent of absorption between the two time periods.
Results
The mean AUC values for serum folate after administration of PregVit® p.m. were 334.5 ± 119.6 nM*h and 283.1 ± 64.3 nM*h for morning and evening, respectively (P = 0.17). The morning and evening peak serum folate concentrations were also similar (135.3 ± 41.7 nM and 130.3 ± 14.2 nM, respectively) (P =0.75). Similarly, the time to peak for the morning arm (1 ± 0.5 hour) was similar to evening administration (1 ± 0.4 hour).
Conclusions
There is no evidence of circadian variation in folate pharmacokinetics. Thus, the introduction of folate in PregVit® p.m. will not affect its effectiveness as compared to its routine administration in the morning.
References
2. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;
338(8760):131-137.
3. Shaw GM, O'Malley CD, Wasserman CR, Tolarova MM, Lammer EJ. Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet 1995; 59(4):536-545.
4. Czeizel AE. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. BMJ 1993; 306(6893):1645-1648.
5. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996; 62(2):179-183.
6. Botto LD, Khoury MJ, Mulinare J, Erickson JD. Periconceptional multivitamin use and the occurrence of conotruncal heart defects: results from a population-based, case-control study. Pediatrics 1996; 98(5):911-917.
7. Li DK, Daling JR, Mueller BA, Hickok DE, Fantel AG, Weiss NS. Periconceptional multivitamin use in relation to the risk of congenital urinary tract anomalies. Epidemiol 1995; 6(3):212-218.
8. Shaw GM, Lammer EJ, Wasserman CR, O'Malley CD, Tolarova MM. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 1995; 346(8972):393-396.
9. Wilson RD, Davies G, Desilets V, Reid GJ, Summers A, Wyatt P et al. The use of folic acid for the prevention of neural tube defects and other congenital anomalies. JOGC 2003; 25(11):959-965.
10. Wald NJ. Folic acid and the prevention of neural- tube defects. N Engl J Med 2004; 350(2):101-103.
11. Wald NJ, Law MR, Morris JK, Wald DS. Quantifying the effect of folic acid. Lancet 2001; 358(9298):2069-2073.
12. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol 1991; 31(3):251-255.
13. Ghishan FK, Said HM, Wilson PC, Murrell JE, Greene HL. Intestinal transport of zinc and folic acid: a mutual inhibitory effect. Am J Clin Nutr 1986; 43(2):258-262.
14. Koren G, Boskovic R, Hard M, Maltepe C, Navioz Y, Einarson A. Motherisk-PUQE (pregnancy- unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. Am J Obstet Gynecol 2002; 186(5 Suppl Understanding):S228-S331.
15. Ahn E, Koren G. The Effects of Nausea and Vomiting of Pregnancy on Compliance with Materna. Can.J.Clin.Pharmacol. 2003; 10[3]:150 (Abstract).
16. Lemmer B. Chronopharmacokinetics: implications for drug treatment. J Pharm Pharmacol 1999; 51(8):887-890.
17. Labrecque G, Belanger PM. Biological rhythms in the absorption, distribution, metabolism and excretion of drugs. Pharmacol Ther 1991; 52(1):95-107.
18. Bruguerolle B. Chronopharmacokinetics. Current status. Clin Pharmacokinet 1998; 35(2):83-94.
19. Wegner C, Nau H. Diurnal variation of folate concentrations in mouse embryo and plasma: the protective effect of folinic acid on valproic-acid- induced teratogenicity is time dependent. Reprod Toxicol 1991; 5(6):465-471.
20. Bothwell TH, Conrad ME, Cook JD, Finch CA. Iron Metabolism in Man. Oxford: Blackwell Scientific Publications, 1979.
21. Rowland M, Tozer T. Clinical pharmacokinetics: concepts and applications. 3rd ed. ed. Baltimore: Williams & Wilkins, 1995.
22. Dawson EB, Evans DR, Conway ME, McGanity WJ. Vitamin B12 and folate bioavailability from two prenatal multivitamin/multimineral supplements. Am J Perinatol 2000; 17(4):193-199.
23. Sifakis S, Pharmakides G. Anemia in Pregnancy. Ann N Y Acad Sci 2000; 900:125-136.
24. Galloway R, McGuire J. Determinants of compliance with iron supplementation: supplies, side effects, or psychology? Soc Sci Med 1994;39(3):381-390.
25. Alward N, Kevany J. Iron Supplementation During Pregnancy: A Survey of the Current Situation. Ir J Med 1984; 77(4):112-114
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.