MEETING REPORT - 24th Population Approach Group Europe (PAGE), 2015


08/06/2015 - PAGE 2015 had various abstracts regarding antifungal agents (itraconazole, fluconazole, anidulafungin and caspofungin)

This year at PAGE, four abstracts were presented on antifungal drugs. These abstracts are listed below:

1. A whole-body physiologically-based pharmacokinetic (PBPK) Model for Itraconazole and its metabolite to predict dynamic drug-drug-interactions

Thomas Wendl et al. Bayer Technology Services GmbH, Leverkusen, Germany

A physiologically-based pharmacokinetic (PB-PK) model for itraconazole and its active metabolite (itraconazole-OH) was developed to predict drug-drug interactions with drugs metabolized by CYP3A4. Midazolam (extensively metabolized by CYP 3A4) was used as a control drug to simulate the impact of itraconazole on its metabolism. The model can be used effectively to predict the pharmacokinetics (PK) of drugs metabolized by CYP3A4 under itraconazole coadministration.

2. Population pharmacokinetic analysis of fluconazole in premature infants

Jaeseong Ooh et al. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea

The pharmacokinetics of fluconazole were studied in 75 premature infants, post menstrual age 21.3-35.7 weeks, treated with 3 mg/kg with an interval of >72 hours for the prevention of invasive candidiasis. Clearance of fluconazole was affected by both renal function (serum creatinine), body weight and post-menstrual age. The model can be used to further optimize dosage regimens of fluconazole in premature infants.

3. Pharmacokinetic/Pharmacodynamic modeling of dynamic time-kill curves for anidulafungin against Candida

Nerea Jauregizar et al. Department of Pharmacology, Faculty of Medicine, University of the Basque Country (UPV/EHU), Spain. UFI11/25 “Microbios y Salud”

Data from an in-vitro infection model of anidulafungin against Candida infections was used together with existing in vivo PK data of anidulafungin to simulate expected time-kill curves for anidulafungin  under typical dosing regimens.  This approach might serve as a model to further define optimal anidulafungin regimens.

4. Dose reduction of caspofungin in ICU patients with Child Pugh B will result in suboptimal exposure

Lisa Martial et al. Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands ; The Netherlands Radboud Institute for Health Sciences, Nijmegen, The Netherlands

A PK model for caspofungin in ICU patients was developed and linked to an existing pharmacodynamic target (AUC/MIC) from a infection mouse-model. Various dosing regimens including both labeled as experimental (higher) doses were tested. Pharmacokinetic target attainment decreased unnecessarily with dose adaptations were made based on Child-Pugh score B (defined as moderate liver impairment) in non cirrhotic ICU patients