RxMed: Pharmaceutical Information - NIZORAL TABLETS In vitro studies suggest that the antifungal properties of ketoconazole may be related to its ability to impair the synthesis of ergosterol, a component of fungal and yeast cell membranes. Without the availability of this essential sterol, there are morphological alterations of the fungal and yeast cell membranes manifested as abnormal membranous inclusions between the cell wall and the plasma membrane. The inhibition of ergosterol synthesis has been attributed to interference with the reactions involved in the removal of the 14-a-methyl group of the precursor of ergosterol, lanosterol. tag_IndicationsIndications Clinical studies in men have shown that single doses of ketoconazole at 200, 400 and 600 mg caused a dose-related decrease in serum testosterone levels, which returned to baseline values 8 to 24 hours later. During chronic administration (12 months) of 200 mg ketoconazole daily, testosterone levels were not significantly suppressed. However, at high doses (1 200 mg a day), administration of ketoconazole resulted in a reduction of serum testosterone to the castrate level (24 ng/dL) within 24 hours; this reduction was maintained for the duration of therapy (3 to 10 months). Oligospermia and azoospermia have been reported at therapeutic doses and above. In 6 healthy females receiving 400 mg once in the late follicular phase and once in the luteal phase, ketoconazole produced a 38% drop in 17-b-estradiol along with a 50% increase in progesterone during the follicular phase as well as a 61% drop in 17-b-estradiol and a 94% increase in progesterone during the luteal phase. Since ketoconazole influences steroid synthesis, the potential for a deleterious effect on puberty and/or fertility must be carefully considered when long-term therapy is contemplated in children.
