Study of the Ability of Clarithromycin to Induce Oxidative Stress
Summary
The purpose of the study is to examine whether Klacid® (Clarithromycin) will induce oxidative stress (stress from oxygen) in healthy subjects. This is done by measuring the content of a particular substance in the urine sample, which is released when the body is exposed to oxidative stress. In addition, there will also be taken blood samples, which is analysed for another substance that is indicative of oxidative stress.
Description
The purpose of the study is to examine whether Klacid® induce oxidative stress in healthy subjects.
Many studies have shown that atherosclerosis can cause acute myocardial infarction (AMI). The development of atherosclerosis is exacerbated by simultaneous infection with Chlamydophila pneumoniae, and its accompanying inflammation. There has been shown a positive association between Chlamydophila pneumoniae antibodies and the incidence of cardiovascular complications, suggesting that Chlamydophila pneumoniae could exacerbate the development of atherosclerosis [1]. It has therefore been tried to treat atherosclerotic AMI- patients prophylactically with macrolide antibiotics (which is used to treat Chlamydia infections), to halt development of the atherosclerosis and the accompanying risk of a new acute myocardial infarction.
Two minor studies have demonstrated a positive effect of macrolide-treatment, why a major Danish study of Clarithromycin was implemented [2-4]. Clarithromycin treatment was tested against placebo in 4373 atherosclerotic patients who had had an AMI. It appeared that the use of clarithromycin led to an increased cardiovascular mortality, which could not be explained [4]. The finding of the study suggests that clarithromycin cannot be used for secondary prophylaxis of cardiovascular complications, but whether clarithromycin can be used for primary prophylaxis is not known.
It has been shown that oxidative stress can participate in the development of cardiovascular complications [5], and it could be such an oxidative stress that had led to the increased mortality in the above study. Especially because a recent american study found evidence that bactericidal antibiotics induce oxidative stress in bacteria, leading to cell death [6]. This oxidative stress contributes significantly to the impact of the bactericidal antibiotics, which was thought to be primarily attributed to their specific drug/target interactions. The same study also examined erythromycin, from which clarithromycin is a derivate. Erythromycin showed no induction of oxidative stress, but clarithromycin is twice as effective as erythromycin, which could be due to oxidative stress caused by clarithromycin.
This study seeks to clarify a possible mechanism for clarithromycin, by an examination on healthy volunteers without atherosclerosis.
Study Design
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Screening
Conditions
Oxidative Stress
Intervention
Clarithromycin
Location
Department of Clinical Pharmacology Q, Rigshospitalet, Blegdamsvej 9
Kopenhagen O
Denmark
2100
Status
Completed
Source
Rigshospitalet, Denmark
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00707330
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Oxidative Stress
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Protein Carbonylation
The appearance of carbonyl groups (such as aldehyde or ketone groups) in PROTEINS as the result of several oxidative modification reactions. It is a standard marker for OXIDATIVE STRESS. Carbonylated proteins tend to be more hydrophobic and resistant to proteolysis.
Tert-butylhydroperoxide
A direct-acting oxidative stress-inducing agent used to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. It is also used as a catalyst in polymerization reactions and to introduce peroxy groups into organic molecules.
Activating Transcription Factor 3
An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.
Heme Oxygenase-1
A ubiquitous stress-responsive enzyme that catalyzes the oxidative cleavage of HEME to yield IRON; CARBON MONOXIDE; and BILIVERDIN.
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