Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs

J Clin Pharmacol. 2014 Dec;54(12):1429-33. doi: 10.1002/jcph.369. Epub 2014 Aug 7.


Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre-specified substudy of a randomized, placebo-controlled trial comparing the antiemetic effect of the doxylamine-vitamin B6 combination (Diclectin®) (n = 131) to placebo (n = 126) in women with nausea and vomiting of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5' phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With Diclectin® exhibiting a significant antiemetic effect in pregnancy, serum concentrations of pyridoxine were unmeasurable in almost all patients and those of pyridoxal were undetectable in half of patients. In contrast, PLP was measurable at sustained, stable steady-state levels in all patients. Our data suggest that there is a correlation between PLP levels and PUQE score of morning sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and hence they might be prodrugs of PLP, which may be the active antiemetic form of vitamin B6.

Trial registration: NCT00614445.

Keywords: morning sickness; nausea and vomiting of pregnancy; prodrug; pyridoxine.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiemetics / blood
  • Antiemetics / pharmacokinetics
  • Antiemetics / therapeutic use*
  • Delayed-Action Preparations
  • Dicyclomine / blood
  • Dicyclomine / pharmacokinetics
  • Dicyclomine / therapeutic use*
  • Double-Blind Method
  • Doxylamine / blood
  • Doxylamine / pharmacokinetics
  • Doxylamine / therapeutic use*
  • Drug Combinations
  • Female
  • Humans
  • Morning Sickness / drug therapy*
  • Morning Sickness / metabolism
  • Pregnancy
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use*
  • Pyridoxal / blood
  • Pyridoxal Phosphate / blood
  • Pyridoxine / blood
  • Pyridoxine / pharmacokinetics
  • Pyridoxine / therapeutic use*


  • Antiemetics
  • Delayed-Action Preparations
  • Drug Combinations
  • Prodrugs
  • dicyclomine, doxylamine, pyridoxine drug combination
  • Pyridoxal
  • Dicyclomine
  • Pyridoxal Phosphate
  • Doxylamine
  • Pyridoxine

Associated data