Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable compound for prophylaxis for those that suffer from chronic vulvovaginal candidiasis. Medical uses
Terconazole is approved to treat vulvovaginal candidiasis (vaginal thrush). It works as a broad spectrum antifungal and has shown to be an effective first-line treatment against other Candida species. It also shows effectiveness against dermatomycoses in animal models.A review found that short-term rates for intravaginally administered azole treatments shows cure in 80% of cases in a short term follow-up and 66% over long term follow-up. In a double-blind study by Slavin in 1992, terconazole showed a 75% mycological cure over a short-term period (7–14 days) and 100% mycological cure over a long-term period (28–34 days). This study focused on the drug as an 80 mg vaginal suppository, taken three times overnight by 10 women. In another placebo-controlled, double blind study by Schmidt et al., the efficacy of different concentrations of terconazole creams were tested. Cream was applied for three days to 24 women between the ages of 18–60. The results showed 0.8% terconazole mycologic cure rates were 83.3% within 1–3 days of starting treatment, 83.3% within 8–11 days of treatment and 58.3% within 30–35 days of treatment.
These are put in a solution and catalyzed using dimethyl sulfate at 1300 °C (2372 °F) to give many different types of triazole derivatives. These are purified using alcohol and chromatography. Terconazole is non-reactive except when exposed to strong oxidizing agents or strong bases due to the nitrogen attached to the triazole ring. It has been found to be photosensitive. Mechanism of action
Terconazole binds to the heme iron component on the cytochrome P450 enzyme lanosterol of fungi, also known as CYP3A4. The gene ERG11 controls lanosterol creation. Lanosterol is found within the yeast plasma membrane. It is a class of methylsterol. Within a normal yeast cell, lanosterol is demethylated using 14α-demethylation. This process creates zymosterol: a major constituent in the ergosterol biosynthesis pathway for the creation of cell membrane constituents in yeast. This structure provides the membrane with fluidity. This occurs by transforming lanosterol into 4,4-dimethyl cholesta-8,14,24-triene-3-β-ol. This stops respiration by prohibiting reduction of NADH to NAD. This stops biosynthesis of cell membrane products as well as transport and catabolism. Eventually, membrane fluidity and activity of membrane bound enzymes become depleted. It has also been shown to inhibit morphologic change of yeast as well as cell adherence and is directly toxic to yeast. Terconazole targets fungi specifically since humans do not use lanosterol in this pathway. This process does not affect all fungi such as Pneumocystis jirovecii, which lacks lanosterol. Metabolism
Absorption of terconazole is 5–8% in patients that have had a hysterectomy and 12–16% in other patients.