Posaconazole exhibits strong anti-tubercular properties. Posaconazole and amiodarone work in concert. In T. cruzi, posaconazole also has an impact on and disturbs Ca2+ homeostasis. The biosynthesis of ergosterol, which is necessary for the survival of parasites, is blocked by posaconazole. Posaconazole, with an IC50 of 14 nM and a minimal inhibitory concentration of 20 nM, clearly affects the proliferation of the epimastigote (extracellular) stages in a dose-dependent manner. Posaconazole is even more effective against the clinically significant intracellular amastigote form of the parasite. The minimal inhibitory concentration (MIC50) of posaconazole is 3 nM, while its half-life is 0.25 nM [1]. Posaconazole is significantly more effective than the other triazoles against zygomycetes and is active against isolates of Candida and Aspergillus species that show resistance to Fluconazole, Voriconazole, and Amphotericin B. [2]

When amiodarone is administered alone to infected animals, it decreases parasitemia, increases survival 60 days after infection (0% for untreated controls vs. 40% for amiodarone-treated animals), and delays the onset of parasitemia when combined with posaconazole[1].
When Posaconazole and Boost Plus are administered together during a fast, the amount of drug exposed to the patient is greater than when Posaconazole is administered alone. Food dramatically raises the bioavailability of posaconazole, especially meals with a high fat content. When posaconazole is taken with a high-fat or nonfat meal, the amount of systemic exposure to the drug increases by 4 and 2.6 times, respectively[3].
Amiodarone and posaconazole could make up a low-side-effect anti-T. cruzi treatment that works well[4].
When administered twice daily at a dose of greater than 15 mg/kg of body weight, posaconazole decreases tissue burden and increases mouse survival[5].

The parasite's epimastigote form is grown in liver infusion tryptose medium,12 with 10% fresh calf serum added, at 28°C and vigorous (120 rpm) agitation. Drugs are added to cultures at a cell density of 0.5−1.0 ×107 epimastigotes mL-1, after they are started at a density of 2×106 epimastigotes mL-1. Both direct counting with a hemocytometer and electronic particle counting are used to measure cell densities.Trypan blue exclusion is used to measure cell viability under light microscopy. As previously mentioned, amastigotes are cultivated in Vero cells kept in minimal essential medium supplemented with 1% fetal calf serum at 37°C in a humidified atmosphere (95% air−5% CO2). After two hours of infection with ten tissue culture-derived trypomastigotes per cell, nonadherent parasites are eliminated by three rounds of phosphate-buffered saline (PBS) washing. The cells are cultured for 96 hours, changing the medium every 48 hours, adding fresh medium both with and without medications. Using light microscopy, the percentage of infected cells and the number of parasites per cell are directly measured. The data are then statistically analyzed as previously mentioned.Using the GraFit program, nonlinear regression is used to calculate IC50 values. Once more using Fura-2, fluorimetric techniques are used to determine the cytoplasmic free Ca2+ concentrations in control and drug-treated extracellular epimastigotes (see previous description). Time-scan confocal microscopy is used to measure the subcellular Ca2+ levels and mitochondrial membrane potentials on individual Vero cells infected with T. cruzi amastigotes; this technique is covered in detail elsewhere. In short, Vero cells had a 72-hour heavy T infection.Cruzi amastigotes are plated onto glass coverslips measuring 22 by 40 mm and have a thickness of 0.15 mm. They are then incubated for 50 minutes at 37°C in culture medium with 10 μM cell-permeant Rhod-2 and 10 μg/mL Rhodamine-123. After this, they are rinsed and incubated with Ringer's solution, either with or without amiodarone. Rhod-2's low affinity for Ca2+ limits its fluorescence in the Ca2+-poor cytoplasm of Vero cells or amastigotes, hence under the conditions used, its fluorescence is primarily derived from intracellular Ca2+-rich compartments, such as mitochondria. A cationic dye called rhodamine-123 is unique to mitochondria and is distributed across the inner membranes in strict accordance with their membrane potential.

The murine model of acute Chagas disease is used for in vivo studies. Female NMRI-IVIC mice (20–25 g) are infected with 105 or 103 bloodstream trypomastigotes, and drug treatment is initiated 24 hours later. For 30 days in a row, treatments consist of 30 doses of posaconazole (20 mg/kg/d) or 15 doses of amiodarone (5 mg/kg every other day).Positive controls are given the anti-T. cruzi drug nifurtimox at a dose of 50 mg/kg/d for 30 days, whereas negative controls, or animals that are not given any treatment, are given just the vehicle. Every day, survival is monitored, and every week, parasitemia is assessed through direct microscopic inspection. After 60 days of observation following infection, parasitological cures are assessed using a combination of blood PCR tests, xenodiagnosis, and hemoculture.

[1]. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem. 2006 Feb 9;49(3):892-9.

[2]. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006 Jun;50(6):2009-15.

[3]. Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers. Antimicrob Agents Chemother. 2006 May;50(5):1881-3. .

[4]. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents. 2012 Jul;40(1):61-71.

[5]. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother. 2002 Jul;46(7):2310-2.

C37H42F2N8O4

700.78

700.33

C, 63.41; H, 6.04; F, 5.42; N, 15.99; O, 9.13

171228-49-2

Posaconazole-d5;1217785-83-5;Posaconazole-d4;1133712-26-1;Posaconazole hydrate;1198769-38-8

Solid powder

FC1=CC=C([C@@]2(CN3C=NC=N3)C[C@H](COC4=CC=C(N5CCN(C6=CC=C(N7C=NN([C@@H](CC)[C@H](C)O)C7=O)C=C6)CC5)C=C4)CO2)C(F)=C1

RAGOYPUPXAKGKH-XAKZXMRKSA-N

InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27+,35-,37-/m0/s1

4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one

Posaconazole; Noxafil; SCH-56592; Schering 56592; Sch 56592; Schering 56592;

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 : 18.75~100 mg/mL ( 26.76~142.69 mM )

10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 1.88 mg/mL (2.68 mM) (Please use freshly prepared in vivo formulations for optimal results.)