Genotoxicity induced by drug-drug interaction between the antidepressant sertraline and the antibiotic erythromycin in mice bone marrow cells. | ||||
| The Egyptian Journal of Hospital Medicine | ||||
| Article 12, Volume 22, Issue 1, January 2006, Page 139-145 PDF (251.69 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ejhm.2006.18036 | ||||
 View on SCiNiTO | ||||
| Author | ||||
| Amany A. Tohamy | ||||
| Zoology Department, Faculty of science, Helwan University | ||||
| Abstract | ||||
| Drug-drug interaction represents a widely distributed health problem. The pharmacological action and side effects of two or more drugs can act additively or antagonistically. The present study was designed to evaluate the possible genotoxicity of concurrent treatment with the antidepressant sertraline, one of the serotonin reuptake inhibitors (SSRI) and the broad spectrum macrolide antibiotic erythromycin. Sertraline and erythromycin are metabolized through CYP3A4 which is one of the cytochrome P-450 enzymes in liver and are responsible for the metabolism of large number of endogenous substrates and therapeutic agents. The frequency of micronucleated polychromatic erythrocytes (MNPCEs), micronucleated normochromatic erythrocytes (MNNCEs) and the ratio PCE/NCE were evaluated to measure the genotoxicity of separate and combined treatment with the tested two drugs. Clinical doses of both sertraline (0.71 mg /kg b.w.) and erythromcyin strearate (14.30 mg / kg b.w.) were used. Groups of animals received single separate or combined doses of either sertraline and/or erythromycin, and sacrificed after 24 hours. Other groups of mice were treated in the same way but for five consecutive days and sacrificed 24 hours after the last injection. In all treated groups, the percentage of PCEs increased significantly when compared with that of the negative control group which may indicate a stimulation of proliferative activity to an early phase of cell depletion. The genotoxicity of multiple treatment for 5 consecutive days with sertraline alone or in combination with erythromcyin was expressed in increased number of MNPCEs. The observed increased genotoxicity after multiple combined treatment with sertraline and erythromycin may indicate increased risk of toxicity-based drug-drug interaction. This toxicity may be due to the ability of sertraline and erythromycin to inhibit the activity of CYP3A4 which lead to a prolonged storage period of drugs in the body and hence increased toxicity. | ||||
| Keywords | ||||
| genotoxicity; Drug-drug interaction; Sertraline; Erythromycin | ||||
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