Pharmacokinetics and Pharmacodynamics of Posaconazole
Open Access
- 22 April 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Drugs
- Vol. 80 (7), 671-695
- https://doi.org/10.1007/s40265-020-01306-y
Abstract
Posaconazole is typically used for preventing invasive yeast and mold infections such as invasive aspergillosis in high-risk immunocompromised patients. The oral suspension was the first released formulation and many pharmacokinetic and pharmacodynamic studies of this formulation have been published. Erratic absorption profiles associated with this formulation were widely reported. Posaconazole exposure was found to be significantly influenced by food and many gastrointestinal conditions, including pH and motility. As a result, low posaconazole plasma concentrations were obtained in large groups of patients. These issues of erratic absorption urged the development of the subsequently marketed delayed-release tablet, which proved to be associated with higher and more stable exposure profiles. Shortly thereafter, an intravenous formulation was released for patients who are not able to take oral formulations. Both new formulations require a loading dose on day 1 to achieve high posaconazole concentrations more quickly, which was not possible with the oral suspension. So far, there appears to be no evidence of increased toxicity correlated to the higher posaconazole exposure achieved with the regimen for these formulations. The higher systemic availability of posaconazole for the delayed-release tablet and intravenous formulation have resulted in these two formulations being preferable for both prophylaxis and treatment of invasive fungal disease. This review aimed to integrate the current knowledge on posaconazole pharmacokinetics, pharmacodynamics, major toxicity, existing resistance, clinical experience in special populations, and new therapeutic strategies in order to get a clear understanding of the clinical use of this drug.This publication has 144 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
- A new solid oral tablet formulation of posaconazole: a randomized clinical trial to investigate rising single- and multiple-dose pharmacokinetics and safety in healthy volunteersJournal of Antimicrobial Chemotherapy, 2012
- Pharmacokinetic/Pharmacodynamic (PK/PD) Indices of Antibiotics Predicted by a Semimechanistic PKPD Model: a Step toward Model-Based Dose OptimizationAntimicrobial Agents and Chemotherapy, 2011
- Pharmacokinetics and Pharmacodynamics of Posaconazole for Invasive Pulmonary Aspergillosis: Clinical Implications for Antifungal TherapyThe Journal of Infectious Diseases, 2011
- Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattiiAntimicrobial Agents and Chemotherapy, 2010
- Therapeutic Drug Monitoring of Posaconazole in Hematology Patients: Experience with a New High-Performance Liquid Chromatography-Based MethodAntimicrobial Agents and Chemotherapy, 2010
- Effect of Varying Amounts of a Liquid Nutritional Supplement on the Pharmacokinetics of Posaconazole in Healthy VolunteersAntimicrobial Agents and Chemotherapy, 2009
- Pharmacokinetics of Posaconazole Administered Orally or by Nasogastric Tube in Healthy VolunteersAntimicrobial Agents and Chemotherapy, 2009
- Pharmacokinetics and Safety of Oral Posaconazole in Neutropenic Stem Cell Transplant RecipientsAntimicrobial Agents and Chemotherapy, 2006