The growth of Candida albicans ATCC 44859 was decreased by terconazole in a concentration-dependent manner. However, the effect was minimal at 0.1 to 10 μM when the yeast was cultured on medium that supported cell morphology. Terconazole's capacity to reduce yeast cell viability differs according on the type and strain of the parasite being examined. Candida albicans ATCC 44859's sensitivity to terconazole was greatly increased when it was cultivated on Eagle's minimal essential medium, which aided in the mycelium's development. The alterations occur in a sequence, starting at 0.1 μM terconazole and ending with total necrosis at 100 μM [1]. At doses of 0.008 to 0.05 μg/mL, terconazole inhibits the morphogenetic transition of yeast to filamentous forms [2].

A 3-day, once-daily intravaginal administration of terconazole 0.8% is typically sufficient to produce a 7-day functional therapeutic period due to the vagina's long-lasting high bioactive antifungal levels. At whatever terconazole concentration, no negative effects were noted [2].

Absorption, Distribution and Excretion
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, excretion of radioactivity was both by renal (32-56%) and fecal (47-52%) routes.

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Metabolism / Metabolites
Systemically absorbed drug appears to be rapidly and extensively metabolized. Terconazole primarily undergoes oxidatative N- and O-dealkylation, dioxolane ring cleavage, and conjugation.

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Biological Half-Life
6.9 hours (range 4.0-11.3)

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Vaginal terconazole has not been studied during breastfeeding. Other antifungal agents may be preferred, especially while nursing a newborn or preterm infant
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
94.9%

[1]. Anticandidal activities of terconazole, a broad-spectrum antimycotic. Antimicrob Agents Chemother. 1986 Jun;29(6):986-91.

[2]. The in vitro activity of terconazole against yeasts: its topical long-acting therapeutic efficacy in experimental vaginal candidiasis in rats. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1200-6.

(2R,4S)-terconazole is a 1-(4-{[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-4-isopropylpiperazine in which positions 2 and 4 of the 1,3-dioxolane moiety have R and S configuration, respectively. It is an enantiomer of a (2S,4R)-terconazole.
Terconazole is an antifungal prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of vulvovaginal candidiasis.
Vulvovaginal candidiasis can be an opportunistic infection (OI) of HIV.
Terconazole is an anti-fungal drug that is mainly used to treat vaginal yeast infections (or vaginal candidiasis). It is classified as a triazole ketal derivative. Terconazole was initially approved by the FDA in 1987. This drug is available in cream and suppository forms and both have demonstrated high levels of safety, efficacy, and tolerability in clinical trials.Due to the existence of 2 stereocentres, there are 4 possible stereoisomers for terconazole.
Terconazole is a synthetic triazole derivative structurally related to fluconazole, antifungal Terconazole seems to disrupt cell wall synthesis by inhibiting biosynthesis of ergosterol or other sterols, damaging the fungal cell membrane, altering its permeability, and promoting loss of essential intracellular elements. Terconazole is active against Candida sp.. (NCI04)

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Drug Indication
For the treatment of candidiasis (a yeast-like fungal infection) of the vulva and vagina.
FDA Label

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Mechanism of Action
Terconazole may exert its antifungal activity by disrupting normal fungal cell membrane permeability. Terconazole and other triazole antifungal agents inhibit cytochrome P450 14-alpha-demethylase in susceptible fungi, which leads to the accumulation of lanosterol and other methylated sterols and a decrease in ergosterol concentration. Depletion of ergosterol in the membrane disrupts the structure and function of the fungal cell leading to a decrease or inhibition of fungal growth.

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Pharmacodynamics
Terconazole is a triazole antifungal agent available for intravaginal use. It is structurally related to imidazole-derivative antifungal agents, although terconazole and other triazoles have 3 nitrogens in the azole ring. By inhibiting the 14-alpha-demethylase (lanosterol 14-alpha-demethylase), Terconazole inhibits ergosterol synthesis. Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth.

C26H31CL2N5O3

532.466

531.18

67915-31-5

Terconazole-d4;1398065-50-3

441383

White to off-white solid powder

1.35g/cm3

681.8ºC at 760mmHg

126.3ºC

366.2ºC

1.64

4.465

0

7

8

36

693

2

CC(C)N1CCN(CC1)C2=CC=C(C=C2)OC[C@H]3CO[C@](O3)(CN4C=NC=N4)C5=C(C=C(C=C5)Cl)Cl

BLSQLHNBWJLIBQ-OZXSUGGESA-N

InChI=1S/C26H31Cl2N5O3/c1-19(2)31-9-11-32(12-10-31)21-4-6-22(7-5-21)34-14-23-15-35-26(36-23,16-33-18-29-17-30-33)24-8-3-20(27)13-25(24)28/h3-8,13,17-19,23H,9-12,14-16H2,1-2H3/t23-,26-/m0/s1

1-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-propan-2-ylpiperazine

R 42,470; R-42,470; R42,470

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 30 mg/mL (~56.34 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)