Imidazole Antifungal Drug Research Articles

Effect of infusion time on the pharmacokinetics of dibekacin in rabbits.

A study was made of the serum levels and of the pharmacokinetic parameters of dibekacin after administration by intravenous infusion at a dose of 2 mg/kg of the drug to rabbits using different infusion times. The peak serum level (Cmax) was seen to decrease progressively on increasing infusion time. The maximum value of Cmax was obtained after administration of the antibiotic by single bolus injection with an average value of 18.297 +/- 9.694 micrograms/ml, while the minimum value was obtained after intravenous infusion over 1 hour, with an average value of 6.597 +/- 1.250 micrograms/ml. A series of linear relationships was established between different pharmacokinetic parameters and the infusion time and a decrease was observed in the pharmacokinetic parameters alpha, K12, K21 and K13 when the infusion time was increased. Changes were also observed in the distribution kinetics of dibekacin in the rabbit on varying the infusion conditions, suggesting alterations in the access and permanence of the antibiotic in tissues.

The effect of imidazoles on germination of arthrospores and microconidia of Trichophyton mentagrophytes.

The effects of imidazole antifungal drugs on germination of Trichophyton mentagrophytes microconidia and arthrospores were investigated. A Coulter Counter was used to estimate spore swelling and microscopy to assess germ-tube formation. Both spore forms germinated in SLM, pH 6, at 32 degrees C and these conditions were used as a control. The inhibition of spore germination by imidazoles was concentration dependent and required higher drug levels than MICs. There was good correlation between reduction in swelling and inhibition of germ-tube formation. In order to produce greater than 90% reduction of germ-tube formation higher concentrations of imidazole were necessary for arthrospores than for microconidia. There was no clear difference in potency of imidazoles except for ketoconazole which was markedly less effective. No increase in sensitivity of microconidia to miconazole was observed with time of addition during the initial 3 h of germination. Although the inhibitory effect of miconazole on swelling of micronidia was partially reduced in the presence of Mg++, germ-tube formation was not altered.

Treatment of experimental murine aspergillosis with BAY n7133.

BAY n7133, a recently developed imidazole antifungal drug, was evaluated in experimental murine aspergillosis. BALB/c mice were challenged with conidia of Aspergillus fumigatus by either the intravenous or the intranasal route. One day after challenge, oral treatment with BAY n7133, ketoconazole, or a placebo control was begun BAY n7133 was well absorbed after oral administration and penetrated all tissues evaluated. There was some evidence for accelerated inactivation of the drug after prolonged therapy. BAY n7133 and ketoconazole both markedly inhibited the growth of mycelia of A fumigatus in vitro. However, only BAY n7133 prolonged the survival time of infected mice. Prolonged survival was associated with a significant reduction in counts of A fumigatus in the lungs. BAY n7133 appeared to be slightly less effective than amphotericin B. In studies with combined drugs, BAY n7133 appeared to add modestly to the benefit conferred by amphotericin B. BAY n7133 seems promising for the treatment of aspergillosis, a disease in which ketoconazole has not been particularly effective.

Miconazole: a preliminary review of its therapeutic efficacy in systemic fungal infections.

Miconazole is an imidazole antifungal drug which has recently become available for systemic use. Its antifungal activity has been well studied and it is active in vitro against a wide range of fungi. Published and unpublished reports of the use of miconazole in conditions such as systemic or mucocutaneous candidosis, coccidioidomycosis, fungal meningitis, and paracoccidioidomycosis (which seems especially responsive) have often been encouraging, particularly in view of the serious, refractory nature of the conditions treated, but in most areas of use experience is limited. There are few effective drugs available for treating most systemic fungal infections, and if further studies confirm the encouraging results often seen to date, miconazole will be an important addition to the limited choices available for such conditions.