Abstract

IN VITRO AND IN VIVO ANTI-HELICOBACTER PYLORI ACTIVITIES OF ZINC AMOXICILLIN COMPLEX: A COMPARATIVE EVALUATION WITH SOME STANDARD ANTIBIOTICS USED IN MULTIPLE THERAPY

Muhammad Amin,*Amin Shah, Muhammad Ramzan Saeed Ashraf Janjua

ABSTRACT

Antibiotic resistance in Helicobacter pylori (H. pylori) is a global threat for human society. Therefore, development of new antimicrobial agents and modification of the existing therapeutic regimens currently being in curing H. pylori related infections is one of the most priority areas of pharmaceutical research. In the present investigation we have modified an active antibiotic, amoxicillin, widely used in curing H. pylori related infections by chelating it with a bio-element, zinc. The synergistic antibacterial activity of zinc complex of amoxicillin (Zn-amox) was tested against 34 clinical isolates and two reference strains of Helicobacter pylori and was compared with parent drug amoxicillin (AMX) and some other antibiotics used in triple therapy against H. pylori like, clarithromycin (CLA), tetracycline (TET) and metronidazole (MNZ). Derivatization of amoxicillin with zinc enhanced the antibacterial activity of the drug by inhibiting the growth of H. pylori as indicated by in vitro and in vivo tests. Zn-amox, exhibiting MICs in the range of .008-0.5 g mL-1, was found stronger anti- H. pylori agent than AMX, CLA, TET and MNZ showing MICs range of 0.125-32, 0.25-8,1- 64 and 1-512 g mL-1, respectively. The complex under study was found equally potent against the antibiotic-resistant and antibiotic-susceptible strains of H. pylori. Furthermore, Zn-amox was found efficacious in the treatment of gastric infection caused by H. pylori in Wistar rates. The complex was found to be far less toxic than the parent drug as demonstrated by its higher LD50 values. The present investigation indicates that the complex is potentially more useful in eradicating both the antibiotic-susceptible and antibiotic-resistant strains of H. pylori and can be developed as a safe and potent single antibiotic for the treatment of H. pylori infection.

Keywords: Zinc-amoxicillin complex, In vivo Helicobacter pylori, In vitro time-dose killing kinetics, gastric ulcer, LD50 values.