Posaconazole

Posaconazole
indication:For prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole is used as an alternative treatment for invasive aspergillosis, Fusarium infections, and zygomycosis in patients who are intolerant of, or whose disease is refractory to, other antifungals.
pharmacologypharmacology:
mechanism: As a triazole antifungal agent, posaconazole exerts its antifungal activity through blockage of the cytochrome P-450 dependent enzyme, sterol 14&alpha;-demethylase, in fungi by binding to the heme cofactor located on the enzyme. This leads to the inhibition of the synthesis of ergosterol, a key component of the fungal cell membrane, and accumulation of methylated sterol precursors. This results in inhibition of fungal cell growth and ultimately, cell death.
toxicity: During the clinical trials, some patients received posaconazole up to 1600 mg/day with no adverse events noted that were different from the lower doses. In addition, accidental overdose was noted in one patient who took 1200 mg BID for 3 days. No related adverse events were noted by the investigator.
absorprion: Posaconazole is absorbed with a median Tmax of approximately 3 to 5 hours.
halflife: Posaconazole is eliminated with a mean half-life (t&frac12;) of 35 hours (range 20 to 66 hours).
roouteelimination: The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.
volumedistribution: * 1774 L
clearance: * 32 L/hr * 51 L/hr [Single-Dose Suspension Administration of 200 mg, fasted] * 21 L/hr [Single-Dose Suspension Administration of 200 mg, nonfat meal] * 14 L/hr [Single-Dose Suspension Administration of 200 mg, high fat meal] * 91 L/hr [Single-Dose Suspension Administration of 400 mg, fasted] * 43 L/hr [Single-Dose Suspension Administration of 400 mg with liquid nutritional supplement (14 g fat)]