RESUMO
Enoxacin is a second-generation quinolone with increased antibacterial activity both in potency as well as in terms of broad spectrum against a wide range of clinically important pathogens over the first generation quinolones and produces its effect by inhibiting bacterial enzyme DNA gyrase. There are a number of drug interactions reported for enoxacin. On the other hand H[2]-receptor antagonists block gastric acid secretion and some cardiovascular effects of histamine. As the later drug are used for a long-term therapy, they may be coadministered with other drugs. In present study in vitro release of enoxacin in presence of cimetidine, ranitidine and famotidine has been studied on a B.P. 2003 dissolution test and compared with the availability of enoxacin and H[2]-receptor antagonists alone. The interacting drugs were analyzed spectrophotometrically. These studies were carried out in simulated gastric juice, simulating empty stomach, simulated intestinal juice [pH 9] and buffers of pH 7.4 simulating blood pH at 37 degree C. In order to support these interaction studies, the effect of H[2]-receptor antagonists on the antibacterial efficacy [MIC] of enoxacin was also studies by turbidity method and compared with parent drug against Staphylococcus aureus, Staphylococcus pyogens, Staphylococcus pneumonia, Enterococcus, Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, Klebsiella pneumonia, Proteus mirabilis and Bacillus subtilis. On the basis of these results, it is suggested that enoxacin should be coadministered with care along with H[2]-receptor antagonists especially in case of ranitidine; although chances of adverse reactions are rare but decrease in MIC of enoxacin may result in delayed effect or require prolonged use of the drug
Assuntos
Antagonistas dos Receptores H2 da Histamina , Interações Medicamentosas , Cimetidina , Ranitidina , Famotidina , Antibacterianos , Testes de Sensibilidade MicrobianaRESUMO
Hydroxymethylglutaryl-coenzyme A reductase inhibitors [statins] are a group of cholesterol lowering agents that have become the largest selling drugs in the world. They are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure [CHF]. Co-administration of statins with angiotensin II receptor blockers [ARBs] is most common, since there is strong synergy between hypertension and hypercholesterolemia in terms of risk factors for the development of cardiovascular diseases. In present paper, we describe the in vitro availability of atorvastatin, a potent HMG-CoA reductase inhibitor, in presence of losartan potassium, which is a non-peptide angiotensin II receptor antagonist. These studies were carried out at 37, 48 and 60 = C in different pH environments simulating human body compartments. It was observed that in pH 1, 7.4 and 9 the availability of atorvastatin was very high while losartan was not at all available. However in pH 4 these effects were reversed and atorvastatin was not available at all. At 48°C the availability of atorvastatin was high and that of losartan was depressed at pH 9, whereas the later was not available at pH 1, 4 and 7.4 at all. Likewise at 60°C, the availability of atorvastatin at pH 7.4 and 9 was high, whereas the charge-transfer complex formed between the two drugs was broken at pH 1 at this temperature and the entire drug was available. On the other hand the availability of losartan at pH 4 and 9 was high while it was not available at pH 1 and 7.4. The availability of atorvastatin was maximum in simulated gastric juice as compared to buffer of pH 7.4 and 9. This high availability of one drug in presence of other is attributed to the formation of a charge-transfer complex, which was stable at elevated temperatures, except at 60°C in pH 1