STUDY ON CIRCADIAN VARIATION IN FOLATE PHARMACOKINETICS

Main Article Content

Eric Ahn
Bhushan Kapur
Gideon Koren

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.

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