Posaconazole (SCH 56592) targets fungal lanosterol 14α-demethylase (CYP51) (IC50 = 0.03–0.12 μM for Aspergillus spp.; IC50 = 0.1–0.5 μM for Candida albicans) [2]
Posaconazole (SCH 56592) inhibits Trypanosoma cruzi proliferation (EC50 = 0.5 μM for T. cruzi epimastigotes; EC50 = 0.4 μM for T. cruzi trypomastigotes) [1][4]

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]

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Posaconazole (SCH 56592) exhibited broad-spectrum antifungal activity against clinically important molds and yeasts: IC50 values for Aspergillus fumigatus (0.03 μM), Aspergillus flavus (0.05 μM), Candida albicans (0.1 μM), Candida glabrata (0.3 μM), and Mucor circinelloides (0.2 μM) [2]
Posaconazole (SCH 56592) exerted anti-Trypanosoma cruzi activity, reducing epimastigote proliferation by 90% at 1 μM and inducing mitochondrial damage (swelling, cristae disruption) in trypomastigotes [4]
Posaconazole (SCH 56592) showed synergistic activity with amiodarone against T. cruzi: combination at 0.25 μM (posaconazole) + 1 μM (amiodarone) resulted in a combination index (CI) of 0.3, achieving 95% proliferation inhibition [1]
Posaconazole (SCH 56592) had no significant cytotoxicity in human PBMCs at concentrations up to 10 μM [1]

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].

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Posaconazole (SCH 56592) improved survival in immunosuppressed mice infected with Mucor spp.: oral administration of 20 mg/kg/day for 10 days increased survival rate from 0% (vehicle) to 70%, reducing fungal load in liver and spleen by 65% [5]
Posaconazole (SCH 56592) did not cause significant weight loss or systemic toxicity in infected mice, with normal serum ALT/AST and creatinine levels [5]

Fungal lanosterol 14α-demethylase (CYP51) inhibition assay: Prepare recombinant fungal CYP51 enzyme and reaction mixture containing lanosterol (substrate), NADPH, and serial dilutions of Posaconazole (SCH 56592) (0.01–5 μM). Incubate at 37°C for 60 min. Extract reaction products with organic solvent, separate by HPLC, and quantify the reduction of 14α-demethylated lanosterol to calculate IC50 [2]

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.

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Antifungal susceptibility assay: Seed fungal spores (Aspergillus spp., Candida spp.) in 96-well plates at 1×104 CFU/well. Add serial dilutions of Posaconazole (SCH 56592) (0.001–10 μM) and incubate at 35°C for 48–72 h. Measure absorbance at 530 nm to assess fungal growth inhibition and calculate IC50 [2]
Trypanosoma cruzi proliferation inhibition assay: Culture T. cruzi epimastigotes/trypomastigotes in 24-well plates at 5×105 parasites/well. Treat with Posaconazole (SCH 56592) (0.1–5 μM) for 72 h. Count parasites using a hemocytometer to determine proliferation inhibition rate and EC50 [1][4]
Synergistic anti-T. cruzi assay: Use checkerboard dilution method to treat T. cruzi epimastigotes with combinations of Posaconazole (SCH 56592) (0.05–2 μM) and amiodarone (0.25–4 μM). Incubate for 72 h, count parasites, and calculate combination index (CI) using the Chou-Talalay method [1]

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.

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Immunosuppressed mouse Mucor infection assay: Male BALB/c mice (6–8 weeks old) are immunosuppressed with cyclophosphamide (150 mg/kg, intraperitoneal) and dexamethasone (10 mg/kg, subcutaneous) 3 days before infection. Mice are intravenously infected with 1×106 Mucor circinelloides spores. One day post-infection, Posaconazole (SCH 56592) is administered via oral gavage at 10 or 20 mg/kg/day for 10 days. The drug is formulated in 0.5% methylcellulose. Survival rate is recorded daily; at study end, liver and spleen are harvested to quantify fungal load via CFU counting [5]

Absorption, Distribution and Excretion
The median time to peak absorption (Tmax) of posaconazole is approximately 3 to 5 hours. Metabolites excreted in urine and feces account for approximately 17% of the administered radiolabeled dose. Pharmacokinetic and protein binding studies of oral posaconazole were conducted in mice infected with neutropenia. Results: 1774 L; 32 L/h; 51 L/h [single dose of 200 mg suspension, fasting]; 21 L/h [single dose of 200 mg suspension, low-fat meal]; 14 L/h [single dose of 200 mg suspension, high-fat meal]; 91 L/h [single dose of 400 mg suspension, fasting]; 43 L/h [single dose of 400 mg suspension followed by 14 g of fluid supplementation]. Within the studied 16-fold dose range, peak concentration and AUC values from 0 hours to infinity exhibited non-linear variations. The serum elimination half-life ranged from 12.0 to 17.7 hours. Compared to tablets, posaconazole suspension improved systemic exposure and relative bioavailability. Food significantly increased the rate and extent of posaconazole absorption in healthy subjects. A total of 103 healthy adults participated in two Phase I clinical trials. Each study employed a double-blind, placebo-controlled, parallel-group design, using either an escalating single-dose (RSD) or escalating multi-dose (RMD) regimen. In the RSD studies, subjects received a single dose of posaconazole oral tablets (50 to 1200 mg) or placebo. In the RMD studies, subjects received posaconazole oral tablets (50 to 400 mg) or placebo twice daily for 14 days. Plasma concentration-time area under the curve and peak plasma concentration were determined using a model-independent method to assess dose proportionality. In the RSD study, posaconazole plasma concentrations increased proportionally within the dose range of 50 to 800 mg, with absorption reaching saturation above 800 mg. Dose-proportionality was also observed in the RMD study. Both studies showed large apparent volumes of distribution (range: 343 to 1341 L) and long terminal half-lives (range: 25 to 31 hours). Subjects fasted for 12 hours before taking the posaconazole oral suspension (800 mg) and again for 48 hours after administration. Dosing regimens included a single dose (Regimen A), 400 mg every 12 hours (Regimen B), or 200 mg every 6 hours (Regimen C). Plasma posaconazole concentrations were measured within 48 hours of the first dose, with a 1-week washout period between treatment regimens. A one-compartment oral model of first-order absorption and first-order elimination was used to fit plasma concentration-time data. Differences in drug exposure were investigated by allowing for variations in bioavailability fractions between dosing regimens. Eighteen healthy men participated in and completed this study. The relative bioavailability of posaconazole differed significantly among different dosing regimens (p < 0.0001) and increased with increasing dosing frequency: Regimen B/Regimen A = 1.98 ± 0.35, an increase of 98%; Regimen C/Regimen A = 3.20 ± 0.69, an increase of 220%. Using a one-compartment model, the population steady-state 24-hour area under the concentration-time curve (AUC) for regimens A, B, and C were predicted to be 3900, 7700, and 12400 μg·h/L, respectively, corresponding to mean plasma concentrations of 162, 320, and 517 μg/L. These data indicate that fractionated dosing (every 12 or 6 hours) significantly increases fasting posaconazole exposure. For more complete data on absorption, distribution, and excretion of posaconazole (6 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Posaconazole circulates primarily in plasma as the parent compound. Among circulating metabolites, most are glucuronide conjugates formed via UDP glucuronidation (a phase II enzyme). Posaconazole has no major circulating oxidative metabolites (CYP450-mediated metabolites). Metabolites excreted in urine and feces account for approximately 17% of the administered radiolabeled dose.

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Biological Half-Life
The mean half-life (t₁₂) of posaconazole is 35 hours (range 20 to 66 hours).
The terminal half-life after intravenous administration is 7 hours in mice and rats, 15 hours in dogs, and 23 hours in monkeys. The oral half-life in rabbits is 9 hours.
Pharmacokinetic and protein binding studies of posaconazole after oral administration were conducted in infected mice with neutropenia. Peak concentrations and AUC values from 0 hours to infinity showed a non-linear variation within the studied 16-fold dose range. The serum elimination half-life of the drug ranged from 12.0 to 17.7 hours. The oral bioavailability of posaconazole (SCH 56592) in fasting healthy volunteers was approximately 29%, which increased to approximately 38% when administered with a nutritional supplement [3]. After oral administration of 400 mg posaconazole (SCH 56592) to healthy volunteers, the peak plasma concentration (Cmax) was 1.2 μg/mL (fasting) and 1.8 μg/mL (with nutritional supplement), with a time to peak concentration (Tmax) of 4–6 hours [3]. The plasma elimination half-life (t1/2) of posaconazole (SCH 56592) in healthy volunteers was 35 hours [3]. Within the oral dose range, the pharmacokinetics of posaconazole (SCH 56592) were dose-proportional. 200–800 mg[3]

Hepatotoxicity
Transient elevations in serum transaminase levels occur in 2% to 12% of patients taking posaconazole. These elevations are usually mild, asymptomatic, and resolve spontaneously, rarely requiring discontinuation of the drug. Clinically significant hepatotoxicity is very rare. The product label mentions the possibility of jaundice and hepatitis during posaconazole treatment, but clinical details are limited. Probability Score: E (Unproven but suspected cause of clinically significant liver injury). Protein Binding Posaconazole has a high protein binding rate (>98%), primarily binding to albumin. Interactions
Currently marketed triazole antifungal drugs typically exhibit drug interactions mediated by multiple CYP450s; however… compared to other triazole drugs, posaconazole may have a more favorable and narrower drug interaction spectrum (interacting only with CYP3A4). This study evaluated the potential pH-dependent pharmacokinetic interactions between posaconazole and an antacid (Mylanta) under fasting and non-fasting conditions. Twelve men completed this randomized, four-period, crossover, single-dose study. Subjects received 200 mg posaconazole after a 10-hour fast, 20 ml Mylanta after a 10-hour fast, 20 ml Mylanta after a 10-hour fast combined with a high-fat breakfast, or a high-fat breakfast alone. Concomitant antacid administration had no statistically significant effect on the bioavailability of posaconazole under either fasting or non-fasting conditions. Under fasting conditions, antacids slightly increased the relative oral bioavailability of posaconazole by 15% (P = 0.296); under non-fasting conditions, antacids decreased the relative oral bioavailability of posaconazole by 12% (P = 0.352). Food increased the relative oral bioavailability of posaconazole by 400% (P = 0.001). In summary, the effect of antacids on posaconazole exposure in fasting or non-fasting states is minimal and clinically insignificant. Posaconazole (SCH 56592) at concentrations up to 10 μM did not show significant cytotoxicity to normal human peripheral blood mononuclear cells [1]. In immunosuppressed mice, doses of posaconazole (SCH 56592) up to 20 mg/kg/day (oral, 10 days) did not cause significant toxicity or weight loss [5]. In healthy volunteers, administration of 400 mg/day of posaconazole (SCH 56592) for 7 consecutive days resulted in <10% of subjects reporting minor adverse events (gastrointestinal discomfort, headache), with no serious toxicity reported [3]. Posaconazole (SCH 56592) is plasma protein bound. Its concentration in human plasma is 98% [2].

[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.

Therapeutic Uses
MeSH Title: Antibiotics, Antifungals, Trypanosomiasis Killers
Drug: Antifungal; Orally Activated Triazole Antifungal
This study evaluated the pharmacokinetics of oral posaconazole suspension in patients with neutropenia who received high-dose chemotherapy and stem cell transplantation, and explored the association between plasma posaconazole exposure and the occurrence and severity of oral mucositis. This was a non-randomized, open-label, parallel-group, multiple-dose pharmacokinetic study. A total of 30 patients were enrolled and received one of three dosing regimens based on the duration of neutropenia (Group I: 200 mg once daily; Group II: 400 mg once daily; Group III: 200 mg four times daily). The mean total exposure on day 1 (expressed as area under the concentration-time curve [AUC(0–24)]) was 1.96 mg·h/L in Group I, and 51% higher in Groups II and III, respectively. The increases in AUC(0-24) and maximum plasma concentration (C(max)) in groups II and III were dose-related. On day 1, AUC(0-24) and C(max) values were similar in groups II and III. Pharmacokinetic parameters showed up to 68% inter-patient variability in this study population. Steady-state was reached on days 5–6. The mean steady-state plasma trough concentrations of posaconazole in groups I, II, and III were 192, 219, and 414 ng/mL, respectively. Both AUC(0-24) and apparent oral clearance increased with increasing dose and dosing frequency. Mucositis appeared to decrease drug exposure, but had no significant effect on the mean total exposure (AUC and Cmax) of posaconazole at steady state (P = 0.1483). Furthermore, increasing the total dose and dosing frequency overcame this decrease. Posaconazole is safe and well-tolerated.
/EXPTL:/ ... Posaconazole has demonstrated potent antifungal efficacy in phase II and III clinical trials of oropharyngeal and esophageal candidiasis in immunocompromised patients. In a large phase II study involving 330 patients with invasive fungal infections that were intolerant to or unresponsive to standard therapy, posaconazole also showed good efficacy as a salvage therapy. ...

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Drug Warning
Invasive fungal infections are most common in immunosuppressed and critically ill hospitalized patients. Long-term antifungal treatment is usually required. This article analyzes safety data from the clinical development program of the triazole antifungal drug posaconazole. In two phase II/III open-label clinical trials, a total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole. Of these, 109 patients received ≥6 months of posaconazole treatment. During the studies, occurrences of treatment-related and serious adverse events, as well as laboratory abnormalities, were recorded. The incidence of treatment-related adverse events was 38%. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). The incidence of treatment-related serious adverse events was 8%. The incidence of treatment-related QT interval prolongation and/or QT interval prolongation (1%) and elevated liver enzymes (2%) was low. The incidence of treatment-related adverse events and treatment-related adverse events was similar in patients who received posaconazole for less than 6 months and those who received it for ≥6 months. Long-term posaconazole treatment was generally well-tolerated in patients with severe refractory invasive fungal infections. Long-term treatment did not increase the risk of any single adverse event, and no specific adverse events were observed due to long-term exposure to posaconazole.
A multicenter, open-label, parallel-group study evaluated the pharmacokinetic characteristics, safety, and efficacy of different dosing regimens of posaconazole oral suspension in patients with suspected, probable, and confirmed refractory invasive fungal infections (rIFI) or febrile neutropenia (FN). Sixty-six patients with febrile neutropenia (FN) and 32 patients with recurrent invasive fungal infection (rIFI) were randomly assigned to one of three posaconazole treatment regimens: Regimen 1, 200 mg four times daily (qid) for nine days, followed by 400 mg twice daily (bid); Regimen 2, 400 mg four times daily (qid) for nine days, followed by 600 mg twice daily (bid); and Regimen 3, 800 mg twice daily (bid) for five days, followed by 800 mg once daily (qd). Treatment for rIFI patients continued for up to 6 months, and treatment for FN patients continued until neutrophils returned to normal. The 400 mg twice daily (bid) dose group had the highest overall mean exposure, which was 135% (P = 0.0004) and 182% (P < 0.0001) higher than the 600 mg twice daily (bid) and 800 mg once daily (qd) dose groups, respectively. However, drug exposure was 52% lower in allogeneic bone marrow transplant (BMT) recipients (n = 12) than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were primarily gastrointestinal reactions. 24% of patients discontinued treatment prematurely due to adverse events (none of which were treatment-independent). In patients with evaluable efficacy, the clinical response rate for recurrent invasive fungal infection (rIFI) was 43% (56% in patients receiving 400 mg bid, 17% in those receiving 600 mg bid, and 50% in those receiving 800 mg qd), and the clinical response rate for febrile neutropenia (FN) was 77% (74% in those receiving 400 mg bid, 78% in those receiving 600 mg bid, and 81% in those receiving 800 mg qd). Posaconazole is well tolerated and well absorbed. Maximum posaconazole exposure is provided by divided doses of 800 mg (400 mg twice daily). The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in patients with mild (creatinine clearance CL(CR) = 50–80 mL/min), moderate (CL(CR) = 20–49 mL/min), and severe chronic kidney disease (CL(CR) <20 mL/min; receiving outpatient hemodialysis) (n = 6 per group). Subjects took a single 400 mg dose of posaconazole oral suspension while taking a standardized high-fat breakfast. For subjects dependent on hemodialysis, this dose was taken on non-dialysis days, with a second 400 mg dose taken 6 hours before hemodialysis. The pharmacokinetics of posaconazole were not correlated with mild to moderate kidney disease. Furthermore, the difference in posaconazole concentration before and after dialysis was only about 3%, indicating that posaconazole is not cleared by hemodialysis.
Pharmacodynamics
Posaconazole is an antifungal drug with a structure related to itraconazole.

It is an itraconazole derivative, in which the chlorine substituent on the benzene ring is replaced by fluorine, and the triazolone side chain is hydroxylated. These modifications enhance the efficacy and antibacterial spectrum of the drug. The mechanism of action of posaconazole can be antifungal or antifungal. Posaconazole (SCH 56592) is a triazole antifungal agent with broad-spectrum activity against molds, yeasts and Trypanosoma cruzi[1][2][4]. Posaconazole (SCH 56592) exerts its antifungal effect by inhibiting fungal lanosterol 14α-demethylase (CYP51), blocking ergosterol synthesis and disrupting the integrity of fungal cell membranes[2]. Posaconazole (SCH 56592) has a synergistic antifungal effect against Trypanosoma cruzi. Amiodarone may inhibit the activity of Cryptospira clarithrum through its combined effects on mitochondrial function [1][4]. Posaconazole (SCH 56592) is clinically indicated for the treatment of invasive fungal infections, particularly in immunocompromised patients [2][5]. Nutritional supplements can improve the oral bioavailability of posaconazole (SCH 56592) by enhancing gastrointestinal absorption [3].

C37H42F2N8O4

700.78

700.329

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

468595

White to off-white solid powder

1.4±0.1 g/cm3

850.7±75.0 °C at 760 mmHg

170-1720C

468.3±37.1 °C

0.0±0.3 mmHg at 25°C

1.658

2.25

1

11

12

51

1170

4

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 )

Solubility in Formulation 1: ≥ 1.88 mg/mL (2.68 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), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 18.8 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1.88 mg/mL (2.68 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 18.8 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: ≥ 1.88 mg/mL (2.68 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 18.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 1.88 mg/mL (2.68 mM)

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