Effect of Concomitant Medications Affecting Gastric pH and Motility on Posaconazole Tablet Pharmacokinetics

Poster presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (52nd ICAAC) held in San Francisco 9/9-9/12 Background: Posaconazole (POS) oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new POS tablet formulation has demonstrated improved bioavailability over oral suspension in healthy adults in the fasting state. This study evaluated the effect of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and motility (metoclopramide) on the pharmacokinetics of POS tablet. Methods: This was a prospective, open-label, 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg (100 mg x 4) dose of POS tablets was administered alone or with 20 mL antacid (Mylanta® Ultimate Strength Liquid, aluminum hydroxide 2 g and magnesium hydroxide 2 g), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was ≥10-day washout between treatment periods. Results: POS exposure, Tmax, and t½ were similar when administered alone or with medications affecting gastric pH and motility. Geometric mean ratios (90% CI) of AUC0-last compared with those of POS alone were antacid, 1.04 (0.90–1.20); ranitidine, 0.97 (0.84–1.12); esomeprazole, 1.02 (0.88–1.17); and metoclopramide, 0.93 (0.80–1.07). Geometric mean ratios (90% CI) of Cmax compared with those of POS alone were antacid, 1.06 (0.90–1.26); ranitidine, 1.04 (0.88–1.23); esomeprazole, 1.05 (0.89–1.24); and metoclopramide, 0.86 (0.73–1.02). Conclusions: In healthy volunteers, the pharmacokinetics of a single dose of POS tablet 400 mg were similar when administered alone or with medications affecting gastric pH or motility

Understanding diabetes in patients with HIV/AIDS

This paper reviews the incidence, pathogenetic mechanisms and management strategies of diabetes mellitus in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). It classifies patients based on the aetiopathogenetic mechanisms, and proposes rational methods of management of the condition, based on aetiopathogenesis and concomitant pharmacotherapy

Amphotericin B lipid complex for neonatal invasive candidiasis

This study describes the safety and efficacy of amphotericin B lipid complex (ABLC) in 11 neonates with systemic Candida infections. Nine of the 11 improved clinically, and eight of nine evaluable patients had a mycological cure with ABLC. Creatinine levels improved or did not significantly change in eight of the 11patients.


Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease

Background: Antifungal prophylaxis with a new oral tablet formulation of posaconazole may be beneficial to patients at high risk for invasive fungal disease. A two-part (Phase 1B/3) study evaluated posaconazole tablet pharmacokinetics (PK) and safety. Methods: Patients with neutropenia following chemotherapy for haematological malignancy or recipients of allogeneic HSCT receiving prophylaxis or treatment for graft-versus-host disease received 300 mg posaconazole (as tablets) once daily (twice daily on day 1) for up to 28 days without regard to food intake. Weekly trough PK sampling was performed during therapy, and a subset of patients had sampling on days 1 and 8. Cmin-evaluable subjects received ≥6 days of dosing, and were compliant with specified sampling timepoints. Steady-state PK parameters, safety, clinical failure and survival to day 65 were assessed. ClinicalTrials.gov, NCT01777763; EU Clinical Trials Register, EUDRA-CT 2008-006684-36. Results: Two hundred and ten patients received 300 mg posaconazole (as tablets) once daily. Among Cmin-evaluable subjects (n = 186), steady-state mean Cmin was 1720 ng/mL (range = 210-9140). Steady-state Cmin was ≥700 ng/mL in 90% of subjects with 5% (10 of 186) <500 ng/mL and 5% (10 of 186) 500-700 ng/mL. Six (3%) patients had steady-state Cmin ≥3750 ng/mL. One patient (<1%) had an invasive fungal infection. The most common treatment-related adverse events were nausea (11%) and diarrhoea (8%). There was no increase in adverse event frequency with higher posaconazole exposure. Conclusions: In patients at high risk for invasive fungal disease, 300 mg posaconazole (as tablets) once daily was well tolerated and demonstrated a safety profile similar to that reported for posaconazole oral suspension: most patients (99%) achieved steady-state pCavg exposures >500 ng/mL and only one patient (<1%) had a pCavg <500 ng/mL