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@ARTICLE{Leithold:279287,
author = {Leithold, Leonie H. E. and Jiang, Nan and Post, Julia and
Ziehm, Tamar and Schartmann, Elena and Kutzsche, Janine and
Shah, N. Jon and Breitkreutz, Jörg and Langen, Karl-Josef
and Willuweit, Antje and Willbold, Dieter},
title = {{P}harmacokinetic {P}roperties of a {N}ovel d-{P}eptide
{D}eveloped to be {T}herapeutically {A}ctive {A}gainst
{T}oxic β-{A}myloid {O}ligomers},
journal = {Pharmaceutical research},
volume = {33},
number = {2},
issn = {1573-904X},
address = {Dordrecht [u.a.]},
publisher = {Springer Science + Business Media B.V},
reportid = {FZJ-2015-07302},
pages = {328-36},
year = {2016},
abstract = {PURPOSE:It has been shown that amyloid β (Aβ) oligomers
play an important role in the pathology of Alzheimer's
disease (AD). D3, a peptide consisting solely of
D-enantiomeric amino acid residues, was developed to
specifically eliminate Aβ oligomers and is therapeutically
active in transgenic AD mice. D-peptides have several
advantages over L-peptides, but little is known about their
pharmacokinetic potential in vivo. Here, we analysed the
pharmacokinetic properties of RD2, a rationally designed and
potent D3 derivative.METHODS:The pharmacokinetic analysis
was performed using 3H-RD2 after administration via several
routes in mice. The time dependent amount of radiolabelled
RD2 was measured in plasma and several organ homogenates by
liquid scintillation counting. Furthermore, binding to
plasma proteins was estimated.RESULTS:RD2 penetrates into
the brain, where it is thought to implement its therapeutic
function. All administration routes result in a maximal
brain concentration per dose (Cmax/D) of 0.06
(μg/g)/(mg/kg) with brain/plasma ratios ranging between 0.7
and 1.0. RD2 shows a small elimination constant and a long
terminal half-life in plasma of more than 2 days. It also
exhibits high bioavailability after i.p., s.c. or p.o.
administration.CONCLUSIONS:These excellent pharmacokinetic
properties confirm that RD2 is a very promising drug
candidate for AD.KEYWORDS:Alzheimer’s disease;
D-enantiomer; peptide; pharmacokinetics; preclinical},
cin = {ICS-6 / INM-4},
ddc = {610},
cid = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)INM-4-20090406},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000368073300007},
pubmed = {pmid:26381279},
doi = {10.1007/s11095-015-1791-2},
url = {https://juser.fz-juelich.de/record/279287},
}