MEETING REPORT - 7th Trends in Medical Mycology (TIMM) 2015

Lisbon, Portugal

26/10/2015 - TIMM 2015 had various abstracts regarding antifungal agents

This year at TIMM, three abstracts were presented on antifungal drugs (regarding drug-drug interactions, pharmacokinetics, and therapeutic drug monitoring). These abstracts are listed below:

1. Drug interction profiles of isavuconazole, voriconazole and posaconazole with immunosuppressants metabolized by CYP4503A4 (CYP3A4)

R. Townsend, A. Desai, N. Azie, M. Jones, M. Engelhardt and A. H. Schmitt-Hoffmann
Astellas Pharma Global Development, Inc, Northbrook, USA and
Basilea Pharmaceutica International Ltd, Basel, Switzerland

A review of clinical pharmacology information was performed to compare the potential for DDIs between immunosuppressants metabolized by CYP3A4 and the triazoles isavuconazole, voriconazole, or posaconazole. The AUC of oral midazolam (probe substrate for CYP3A4) was increased 2-fold with isavuconazole, 5-fold with posaconazole and 10-fold with voriconazole. Results with immunosuppressants metabolized by CYP3A4 were presented in a table. It was concluded that, considering midazolam probe substrate, isavuconazole exhibits moderate inhibition of CYP3A4 (2 and <5 -fold), whereas posaconazole and voriconazole are strong CYP3A4 inhibitors (5-fold). Clinical pharmacology studies demonstrated that the effect of isavuconazole on CYP3A4 substrates is substantially less pronounced than posaconazole or voriconazole. The clinical pharmacology profile indicates potential advantages of isavuconazole in treating patients receiving immunosuppressants metabolized by CYP3A4.

2. Posaconazole Pharmacokinetics among Lung Transplant Recipients

C. Clancy, M. H. Nguyen, E. Press and R. K. Shields
University of Pittsburgh, Pittsburgh, USA

A prospective study of posaconazole oral suspension PK among lung transplant recipients with or without CF was conducted. It was concluded that posaconazole levels were suboptimal among lung transplant recipients, particularly those with CF. Trough levels are representative of steady state AUC and ideal for therapeutic drug monitoring. Given the challenging PK of posaconazole oral suspension in this population, there is a pressing need to study PK of new formulations. 

3. Voriconazole blood levels and its major metabolite, voriconazole-N-oxide: Utility on Therapeutic Drug

A. Gomez-Lopez, L. Bernal-Mart─▒nez and A. Alastruey-Izquierdo
CNM-ISCIII, Majadahonda, Spain and Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain

A study was conducted to develop and validate a chromatographic method to detect and quantify voriconazole and its major metabolite in serum samples, valid for estimating individual metabolic rate. Also, this study described the metabolic rate from serum samples received in our department to monitor voriconazole concentrations. It was concluded that the method allows the simultaneous quantification of VRC and its major metabolite VRC-NO in serum samples. The estimation of the metabolite/active drug relationship
could quickly detect patients with impaired voriconazole metabolism.