In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 60, No. 2 ( 2010-02-18), p. 171-178
Abstract:
The plasma pharmacokinetics and brain uptake of the novel neuroprotective agent AM-36 (1-(2-(4-chlorophenyl)-2-hydroxy)ethyl-4-(3,5-bis-(1, 1dimethylethyl)-4-hydroxyphenyl) methylpiperazine) were assessed over 72 h following i.v. administration to male Sprague-Dawley rats. At nominal i.v. doses of 0.2, 1 and 3 mg kg−1, AM-36 exhibited an extremely large volume of distribution (18.2–24.6 L kg−1) and a long terminal elimination half-life, ranging from 25.2 to 37.7 h. Over this dose range, AM-36 exhibited linear pharmacokinetics, with no apparent change in clearance, volume of distribution or dose-normalised area under the plasma concentration-time curve. AM-36 was very highly bound to plasma proteins ( & gt; 99.6%); however, this did not appear to affect the ability of AM-36 to permeate the blood-brain barrier. Following a single i.v. dose of AM-36 at 3 mg kg−1 to rats, brain concentrations were detected for up to 72 h, and the brain-to-plasma ratios were high at all time points (ranging from 8.2 at 5 min post-dose to 0.9 at 72 h post-dose). The very high brain uptake of AM-36 supports previous in-vivo efficacy studies demonstrating the neuroprotective effects of this compound when administered to rats with middle cerebral artery occlusion.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/jpp.60.2.0005
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
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