] [76] [77] [83] Reference [40]Pharmaceutics 2021, 13,13 of4. Posaconazole Posaconazole is a representative from the second generation triazole antifungal agent using a broad spectrum of antifungal activity. It can be indicated inside the therapy of invasive fungal infections for instance aspergillosis, fusariosis, and zygomycosis. Inside the European Union, it is approved to treat refractory IFI as a first-line agent in oropharyngeal candidiasis. In the US, it is utilised for the prophylaxis of Aspergillus and Candida infections refractory for itraconazole and/or fluconazole. The other indication for posaconazole therapy is oesophageal or febrile neutropenia, plus the lack of effects or intolerance for other antifungal therapy [87,88]. It truly is obtainable on the market within the strong formulation as tablets or in liquid form (as suspension) [10]. The therapeutic dose is 800 mg/day administered BID; nonetheless, the variety is broad–it comprises 5000 mg. A additional improve inside the serum concentration is just not observed for the dose that exceeds 800 mg. Its bioavailability depends upon the formulation. It increases for the suspension along with the fed state [87,89]. The elimination half-life amounts to 31 h [90]. The higher volume of distribution, 500 L, suggests extensive tissue distribution. The maximum concentration is reached immediately after 3 h post administration, plus the steady-state is reached just after 7 to 10 days [88]. It includes a strong affinity to proteins–it is bound in 95 [91]. 4.1. Influence of Food and pH inside the Gastrointestinal Tract on the PI3KC2β Molecular Weight Absorption of Posaconazole The fasting state influences the bioavailability of posaconazole. Courtney et al. and Sansone-Parsons et al. [89,92] examined the effect of meals and nutritional supplements on the pharmacokinetics of posaconazole in healthful patients. In the study carried out by Courtney et al. [89], a single oral dose of posaconazole 200 mg/5 mL inside a suspension with each NOP Receptor/ORL1 supplier high-fat and non-fat breakfasts, and after 10 h rapidly. The tablets (two 100 mg) had been administered using a high-fat meal. The evaluation with the pharmacokinetic parameters showed that high-fat and non-fat meals enhanced the relative bioavailability from the posaconazole suspension over 290 and 168 , respectively. The absorption rate remained on the identical level. The pharmacokinetic profiles for tablets provided with fatty meals and the suspension given with non-fat meals have been similar. The pharmacokinetic profile for a tablet offered having a fatty meal was equivalent towards the one particular given within a suspension using a non-fat meal. This implies that both coadministration with food irrespective of the fat content, and within the kind of suspension would be the important variables that influence the exposure of the patient to the drug. The suspension is far more practical for sufferers that have troubles with swallowing [89]. SansoneParsons et al. examined the effect of nutrition supplements on the pharmacokinetic parameters of posaconazole. The coadministration of your drug suspension (400 mg/10 mL) with a nutrition supplement led to a rise of AUC and Cmax. The half-life and tmax remained on the identical level. These studies indicated that posaconazole really should be administered with meals, no matter each the kind of meals (strong or liquid) along with the fat content (non-fat vs. high fat) [89,92]. Antifungal agents for example ketoconazole and itraconazole are weak bases. Posaconazole is structurally connected to itraconazole and has related physicochemical properties. Carlson et al. investigated the solubility of ketoconazole in many pH, a