CLINICAL PHARMACOLOGY
Following intravaginal administration of terconazole in humans, absorption ranged from 5-8 % in three hysterectomized subjects and 12-16 % in two non-hysterectomized subjects with tubal ligations.
Following oral (30 mg) administration of 14C-labelled terconazole, the harmonic half-life of elimination from the blood for the parent terconazole was 6.9 hours (range 4.0-11.3). Terconazole is extensively metabolized; the plasma AUC for terconazole compared to the AUC for total radioactivity was 0.6 %. Total radioactivity was eliminated from the blood with a harmonic half-life of 52.2 hours (range 44-60). Excretion of radioactivity was both by renal (32-56 %) and fecal (47-52 %) routes.
In vitro, terconazole is highly protein bound (94.9 %) and the degree of binding is independent of drug concentration.
Photosensitivity reactions were observed in some normal volunteers following repeated dermal application of terconazole 2.0% and 0.8% creams under conditions of filtered artificial ultraviolet light.
Photosensitivity reactions have not been observed in U.S. and foreign clinical trials in patients who were treated with terconazole vaginal cream 0.4%.
Microbiology: Terconazole exhibits fungicidal activity in vitro against Candida albicans. Antifungal activity has also been demonstrated against other fungi. The MIC values of terconazole against most Lactobacillus spp. typically found in the human vagina were ≥ 128 mcg/mL; therefore these beneficial bacteria are not affected by drug treatment. The exact pharmacologic mode of action of terconazole is uncertain; however, it may exert its antifungal activity by the disruption of normal fungal cell membrane permeability. No resistance to terconazole has developed during successive passages of C. albicans.
|
