A pharmacokinetic study of pyridoxal-5*-phosphate and pyrixodine

Vitamin B6 supplementation has been found to induce neurotoxic effects
(neuropathies). Animal models and recent in vitro studies in human neuronal
cells indicated that the toxicity of vitamin B6 is specifically limited to one
vitamer, i.e. pyridoxine (PN). Other vitamers, pyridoxal (PL), pyridoxal-5*-
phosphate (PLP) and pyridoxamine (PM) did not induce toxic effects. Moreover,
in vitro studies indicated that neurotoxicity of PN was reversed when PLP is
administered simultaneously (Vrolijk et al., manuscript submitted, appendix 1).
Currently, most vitamin supplements contain PN, but based on its neurotoxicity
it appears preferable to use one of the other vitamers. This implies the
assumption that the other vitamers will not induce increased plasma levels of
PN, thereby greatly reducing the risk of developing neuropathies. It is not
yet investigated whether the use of PLP-containing supplements can lead to
increased plasma levels of PN.

The aim of this study is to compare the pharmacokinetics of
pyridoxal-5'-phosphate (PLP) and pyridoxine (PN) immediately after
administration of a dose of 50 mg. In addition, plasma levels of B6 vitamers
after three and seven days intake of 50 mg/day of either PLP or PN will be
detemined.

Using a double blind randomized design, pharmacokinetics of 50 mg
pyridoxal-5'-phosphate (PLP) and 50 mg pyridoxine (PN) will be followed during
4 hours after administration to healthy adult males and females. Every 30 min.
venous blood will be sampled (iv-canule) for analysis of plasma levels of PN
and other B6 vitamers using LC-MS-QTOF. In addition, after 3 and after 7 days
(1 week) daily administration of either 50 mg PY or 50 mg PLP venous blood will
be sampled by venapuncture for analysis of plasma levels of PN and other B6
vitamers.

This study is a pharmacokinetic study in which healthy adults will daily
receive 50 mg pyridoxal-5'-phosphate (PLP) or 50 mg pyridoxine (PN) during 1
week.

Participants of this study will receive 50 mg pyridoxal-5'-phophate (PLP) or 50
mg pyridoxine (PN) daily during one week (capsules) and venous blood samples
will be taken on specific occasions: during screening for measurement of liver
and kidney functions; during the pharmacokinetic study 9 venous blood samples
of 5 ml (iv-canule) will be collected and after 3 and 7 days of supplementation
a venous blood sample of 5 ml will be collected by venapuncture; a total of 50
ml venous blood will be sampled within 1 week. The risks involved are
considered minimal and limited to potential problems that may occur venous
blood sampling such as the development of hematomas. The daily supplementation
with 50 mg of either PLP or PN during one week is too short to induce
neurologic problems or neurotoxic effects. Results of this study will provide
information that contributes to the save use of vitamin B6 supplements.