Safety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase I Randomized Clinical Trial in Healthy Humans

Simple item page
dc.contributor.authorGajardo Cortez, Abraham I. J.
dc.contributor.authorLillo-Moya, Jose
dc.contributor.authorSan-Martin-Martinez, Daniel
dc.contributor.authorPozo-Martinez, Josue
dc.contributor.authorMorales, Pablo
dc.contributor.authorPrieto, Juan C.
dc.contributor.authorAguayo, Ruben
dc.contributor.authorPuentes, Angel
dc.contributor.authorRamos, Cristobal
dc.contributor.authorSilva, Solange
dc.contributor.authorCatalan, Mabel
dc.contributor.authorRamos, Karla
dc.contributor.authorOlea-Azar, Claudio
dc.contributor.authorRodrigo, Ramon
dc.date.accessioned2025-01-20T16:13:39Z
dc.date.available2025-01-20T16:13:39Z
dc.date.issued2024
dc.description.abstractMyocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.
dc.description.funderAgencia Nacional de Investigacion y Desarrollo
dc.fuente.origenWOS
dc.identifier.doi10.1002/cpdd.1443
dc.identifier.issn2160-7648
dc.identifier.urihttps://doi.org/10.1002/cpdd.1443
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90398
dc.identifier.wosidWOS:001264970500001
dc.issue.numero9
dc.language.isoen
dc.pagina.final1060
dc.pagina.inicio1051
dc.revistaClinical pharmacology in drug development
dc.rightsacceso restringido
dc.subjectantioxidants
dc.subjectascorbic acid
dc.subjectcombined antioxidant therapy
dc.subjectdeferoxamine
dc.subjectN-acetylcysteine
dc.subjectoxidative stress
dc.subjectpharmacokinetics
dc.subjectPhase I
dc.subjectsafety
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSafety and Pharmacokinetics of a Combined Antioxidant Therapy against Myocardial Reperfusion Injury: A Phase I Randomized Clinical Trial in Healthy Humans
dc.typeartículo
dc.volumen13
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas