Update on Posaconazole Pharmacokinetics: Comparison of Old and New Formulations

Gastrointestinal and Systemic Monitoring of Posaconazole in Humans After Fasted and Fed State Administration of a Solid Dispersion

“…[13][14][15] Clinical studies revealed that this tablet outperforms the oral suspension in terms of posaconazole absorption, without the need for food intake to maximize bioavailability. [16][17][18][19] Although it is believed that the molecularly dispersed posaconazole will create a state of supersaturation along the gastrointestinal tract to improve intestinal absorption, it is still questionable how physiological variables will determine or influence gastrointestinal concentrations of posaconazole along the GI tract after oral intake. Therefore, the aim of this study was to assess the impact of this formulation type on different gastrointestinal processes (e.g., drug release, dissolution, supersaturation, precipitation, and intestinal absorption) by monitoring the gastrointestinal behavior and systemic exposure of posaconazole, after administration of the delayed-release solid dispersion to healthy volunteers (HVs), in both the fasted and fed state condition.…”

Drug disposition before and after gastric bypass: fenofibrate and posaconazole

“…Both fenofibrate and posaconazole are lipophilic drugs and may be associated with an increase in V D before RYGB as obesity is associated with an excessive fat mass accumulation. Posaconazole, in particular, has a remarkable distribution in the body; one study found a 40‐fold higher concentration in the tissue than in the serum . We have shown that the fat mass percentage after surgery was significantly decreased, which might have resulted in a decreased V D post‐RYGB.…”

Antifungal Agents

“…Absorption of posaconazole suspension is dose limited at 800 mg/day and can be improved if the suspension is administered with a high-fat meal or in divided doses (twice to four times daily; Table 7.2; [44]). A more recently introduced delayed-release tablet formulation uses pH-sensitive polymers to release posaconazole at a controlled rate in the duodenum, thereby circumventing many of the problems associated with poor gastric dissolution of the drug [45]. As a result, following a loading dose (300 mg twice daily on day 1), the average serum concentration achieved with a 300-mg daily dose using delayed-release posaconazole tablets is 1400 ng/mL, which is more than double of that achieved with the oral suspension administered at 200 mg four times daily (517 ng/mL; [45,46]).…”

“…A more recently introduced delayed-release tablet formulation uses pH-sensitive polymers to release posaconazole at a controlled rate in the duodenum, thereby circumventing many of the problems associated with poor gastric dissolution of the drug [45]. As a result, following a loading dose (300 mg twice daily on day 1), the average serum concentration achieved with a 300-mg daily dose using delayed-release posaconazole tablets is 1400 ng/mL, which is more than double of that achieved with the oral suspension administered at 200 mg four times daily (517 ng/mL; [45,46]). The tablet formulation also provides the opportunity to administer a loading dose on the first day of therapy to ensure therapeutic posaconazole plasma levels in the first 24-48 h. This is in contrast with the oral suspension, which typically would not approach steady-state therapeutic levels until 7-10 days of therapy [47].…”

“…Dosing is similar to the oral delayed-release tablets (300 mg was administered intravenously twice on day 1 followed by 300 mg daily) and achieved trough concentrations greater than 1000 ng/mL within 24 h in a majority of patients [45,46]. The intravenous formulation is preferred in critically ill patients or patients who cannot swallow the tablet formulations, which cannot be crushed.…”