Sökning: onr:"swepub:oai:DiVA.org:uu-443967" >
Phase 1 study to ac...
Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers
-
- Al-Mahdi Al-Karagholi, Mohammad (författare)
- Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark
-
- Møller Hansen, Jakob (författare)
- Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark; Rigshosp Glostrup, Danish Knowledge Ctr Headache Disorders, Glostrup, Denmark
-
- Abou-Kassem, Dalia (författare)
- Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark
-
visa fler...
-
- Koldbro Hansted, Anna (författare)
- Univ Copenhagen, Rigshosp Glostrup, Fac Hlth & Med Sci, Glostrup Res Inst,Danish Headache Ctr, Glostrup, Denmark
-
- Ubhayasekera, Kumari (författare)
- Uppsala universitet,Analytisk kemi
-
- Bergquist, Jonas (författare)
- Uppsala universitet,Analytisk kemi
-
- Vécsei, László (författare)
- Univ Szeged, Dept Neurol, Szeged, Hungary; Univ Szeged, MTA SZTE Neurosci Res Grp, Szeged, Hungary
-
- Jansen-Olesen, Inger (författare)
- Univ Copenhagen, Rigshosp Glostrup, Fac Hlth & Med Sci, Glostrup Res Inst, Danish Headache Ctr, Glostrup, Denmark
-
- Ashina, Messoud (författare)
- Univ Copenhagen, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark; Rigshosp Glostrup, Danish Knowledge Ctr Headache Disorders, Glostrup, Denmark
-
visa färre...
-
(creator_code:org_t)
- 2021-03-07
- 2021
- Engelska.
-
Ingår i: Pharmacology Research & Perspectives. - : John Wiley & Sons. - 2052-1707. ; 9:2
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://onlinelibrar...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- epilepsy
- glutamat
- kynurenic acid
- migraine
- stroke
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas