This study measured the time courses of concentration changes following administration of the catalytic
antioxidants Mn (III) tetrakis (4-benzoic acid)
porphyrin (
MnTBAP) and Mn (III) 3-methoxy N, N' bis (salicyclidene)
ethylenediamine chloride (EUK-134) in blood and cerebrospinal fluid (CSF) of rats with a
spinal cord injury (SCI) and
sham controls. Parallel measurements were made for
methylprednisolone, the only
drug presently used clinically for treating SCI. The time courses kinetically characterized the agents in their stability, disposition, and ability to penetrate the blood-spinal cord barrier (BSB). In both the SCI and control groups,
MnTBAP was stable in CSF and in blood across the collection periods (10 h and 24 h, respectively) following administration. In the blood, [EUK-134] and [
methylprednisolone] rapidly declined to near basal concentrations at 4 h and 2 h, respectively, post-administration. Therefore the order of stability in CSF and blood was
MnTBAP >>
EUK-134 >
methylprednisolone. The maximum CSF/blood concentration ratios for
EUK-134,
methylprednisolone and
MnTBAP post-administration were: 32 ± 3.1%, 19.2 ± 6.4%, and 4.42 ± 0.73% in the injured rats, and 22 ± 6.5%, 17.8 ± 2.9%, and 1.0 ± 0.5% in the
sham control animals. This suggests an order of BSB penetration of
EUK-134 >
methylprednisolone >>
MnTBAP. Despite much lower penetration by
MnTBAP compared with
EUK-134 and
methylprednisolone, a lower dose of
MnTBAP because of its stability provided a higher concentration in CSF than did the other agents given at higher doses. This finding supports further exploration of
MnTBAP as a potential treatment for SCI.