255 Journal of Basic and Clinical Pharmacy www.jbclinpharm.com IN-VITRO EFFECTS OF CADMIUM, CHROMIUM, MANGANESE AND ZINC ON THE ANTIMICROBIAL ACTIVITY OF CHLORAMPHENICOL A. Musa 1 *, I. A. Yakasai 1 , M. Garba 1 , B. O. Olayinka 2 and C. Udekwe 1 1 Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria 2 Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria ABSTRACT: Heavy metals have been shown to interact with various antibiotics result- ing in differing spectrum of activity than that of the parent drug. In the present study the nature of antimicrobial activity exhibited by chloramphenicol in the presence of Cd, Cr, Mn and Zn at 37°C against S. typhii, S. aureus, E. coli, P. vulgaris and K. pneumo- niae were evaluated. Broth dilution method of antimicrobial susceptibility testing was used to determine the minimum inhibitory concentration (MIC) of chloramphenicol against the organisms, while the cup-plate agar diffusion technique was used to quan- tify antimicrobial activity of the free drug and drug-metal mixtures. Results obtained for the interactions showed both decrease and increase in chloramphenicol activity depending on the type and concentration of the metal involved, and also on the or- ganism. The resultant change in spectrum and profile of activity can result in unpre- dictable clinical efficacy of this drug and they should be avoided where possible. KEYWORDS: chloram- phenicol, heavy metals, complexation, interaction, zone of inhibition INTRODUCTION C hloramphenicol is a broad spectrum an- tibiotic which was first isolated from cul- tures of Streptomyces venezuelae but is now produced synthetically. he preferred chemical name is D-threo-2,2-dichloro-N-[3-hydroxy-a- (hydroxymethyl)-p-nitrophenethyl]-acetamide (Figure 1). It is a derivative of dichoroacetic acid with a nitrobenzene moiety attached and it acts by interfering with bacterial protein synthesis. It is mainly bacteriostatic with a broad spectrum of ac- tion against both Gram positive and Gram negative bacteria, as well as some other organisms includ- ing rickettsiae and chlamydias [1]. he risk of life threatening adverse effects (particularly bone mar- row aplasia) and resistance, has severely limited the clinical usefulness of chloramphenicol [1]. It is how- ever experiencing resurgence in use in some coun- tries due to resistance to other safer antibiotics and its superiority in fighting certain anaerobic infections and infections of the central nervous system [2]. Metal complexes with active pharmaceuticals in which the drug molecules play the role of a ligand have been reported [3,4,5]. he nitro group, alkyl hydroxyl groups and the amide nitrogen in chloramphenicol also act as suitable ligand and metal binding sites for formation of dative covalent bonds with heavy metals [6,7,8,9]. As a result of such interactions, metal ions have been reported to significantly alter the activity of different drugs especially antibiotics [10,11,12]. *Corresponding Author: E-mail: aminu.musa39@yahoo.com received on 19-07-2010 modified on 22-08-2010 accepted on 03-09-2010 available online15-11-2010 www.jbclinpharm.com Figure 1: Chloramphenicol