Phase 1B Study of the Pharmacokinetics and Safety of Posaconazole Intravenous Solution in Patients at Risk for Invasive Fungal Disease
Open Access
- 1 July 2014
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 58 (7), 3610-3617
- https://doi.org/10.1128/aac.02686-13
Abstract
This was a phase 1B, dose-ranging, multicenter, pharmacokinetics, and safety study of cyclodextrin-based posaconazole intravenous (i.v.) solution administered through a central line to subjects at high risk for invasive fungal disease (part 1 of a 2-part study [phase 1B/3]). Initially, the safety and tolerability of single-dose posaconazole i.v. 200 mg (n = 10) were compared with those of a placebo (n = 11). Subsequently, 2 doses were evaluated, posaconazole i.v. 200 mg once daily (q.d.) (n = 21) and 300 mg q.d. (n = 24). The subjects received twice-daily (b.i.d.) posaconazole i.v. on day 1, followed by 13 days of posaconazole i.v. q.d., then 14 days of posaconazole oral suspension 400 mg b.i.d. The steady-state (day 14) exposure target (average concentration [areas under concentration-time curve {AUCs}/24 h, average concentrations at steady state {Cavgs}], of ≥500 to ≤2,500 ng/ml in ≥90% of the subjects) was achieved by 94% of the subjects for 200 mg posaconazole q.d. and by 95% of subjects for 300 mg posaconazole q.d. The desired exposure target (mean steady-state Cavg, ∼1,200 ng/ml) was 1,180 ng/ml in the 200-mg dosing cohort and was exceeded in the 300-mg dosing cohort (1,430 ng/ml). Posaconazole i.v. was well tolerated. Posaconazole i.v. 300 mg q.d. was selected for the phase 3 study segment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01075984.)Keywords
This publication has 20 references indexed in Scilit:
- Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting ConcentrationAntimicrobial Agents and Chemotherapy, 2012
- Single-Dose Phase I Study To Evaluate the Pharmacokinetics of Posaconazole in New Tablet and Capsule Formulations Relative to Oral SuspensionAntimicrobial Agents and Chemotherapy, 2012
- Posaconazole Exposure-Response Relationship: Evaluating the Utility of Therapeutic Drug MonitoringAntimicrobial Agents and Chemotherapy, 2012
- Pharmacokinetics of Different Dosing Strategies of Oral Posaconazole in Patients with Compromised Gastrointestinal Function and Who Are at High Risk for Invasive Fungal InfectionAntimicrobial Agents and Chemotherapy, 2012
- Exposure–Response of Posaconazole Used for Prophylaxis Against Invasive Fungal Infections: Evaluating the Need to Adjust Doses Based on Drug Concentrations in PlasmaClinical Pharmacology & Therapeutics, 2010
- Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy VolunteersAntimicrobial Agents and Chemotherapy, 2009
- Posaconazole as Salvage Treatment for Invasive Fusariosis in Patients with Underlying Hematologic Malignancy and Other ConditionsClinical Infectious Diseases, 2006
- PosaconazoleDrugs, 2005
- Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adultsBritish Journal of Clinical Pharmacology, 2003
- Options for artificial nutrition of cancer patients.1998