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| Hauptseite > Publikationsdatenbank > Pharmacokinetic Properties of a Novel d-Peptide Developed to be Therapeutically Active Against Toxic β-Amyloid Oligomers > print |
| Hauptseite > Publikationsdatenbank > Pharmacokinetic Properties of a Novel d-Peptide Developed to be Therapeutically Active Against Toxic β-Amyloid Oligomers > print |
| 001 | 279287 | ||
| 005 | 20210129221028.0 | ||
| 024 | 7 | _ | |a 10.1007/s11095-015-1791-2 |2 doi |
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| 041 | _ | _ | |a English |
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| 100 | 1 | _ | |a Leithold, Leonie H. E. |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Pharmacokinetic Properties of a Novel d-Peptide Developed to be Therapeutically Active Against Toxic β-Amyloid Oligomers |
| 260 | _ | _ | |a Dordrecht [u.a.] |c 2016 |b Springer Science + Business Media B.V |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1453737283_6240 |2 PUB:(DE-HGF) |
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| 520 | _ | _ | |a 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 |
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| 773 | _ | _ | |a 10.1007/s11095-015-1791-2 |0 PERI:(DE-600)2036232-8 |n 2 |p 328-36 |t Pharmaceutical research |v 33 |y 2016 |x 1573-904X |
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