Pharmacogenomics of the triazole antifungal agent voriconazole.

Genetic polymorphisms in drug-metabolizing enzymes are frequently responsible for high variability in the pharmacokinetics of certain drugs leading to large variations in drug efficacy and adverse drug effects, or large ranges of the doses required for optimal drug efficacy. Voriconazole is a triazole antifungal agent which has been available for several years and has potent in vitro and in vivo activity against a broad spectrum of medically important pathogens, including Aspergillus, Cryptococcus and Candida. Voriconazole is extensively metabolized by the cytochrome P450 system with CYP2C19 being the major route for elimination.

New mutation in the CYLD gene within a family with Brooke-Spiegler syndrome.

Brooke-Spiegler syndrome is a rare, autosomal dominant disease characterized by multiple skin appendage tumors caused by various mutations in the CYLD gene on chromosome 16q12-q13. We describe a family, in which we performed a molecular-genetic examination and found a new mutation in exon 19 in the CYLD gene leading to a frameshift. It is important to be aware of this syndrome and its pathogenesis as its phenotypic features can vary so that apparently different diseases are caused by the same genetic defect.

Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype.

What Is Already Known About This Subject: * Pharmacokinetic variability of voriconazole is largely caused by CYP3A4- and CYP2C19-mediated metabolism. * Oral bioavailability of voriconazole has been claimed to be almost 100%, thus facilitating a change from intravenous to oral application without dose adjustment.

What This Study Adds: * For the first time voriconazole exposure after intravenous and oral administration in relation to CYP2C19 activity is reported.

Primary mucinous eccrine carcinoma of the skin--a rare clinical tumor with many differential diagnoses.

Primary mucinous eccrine carcinoma of the skin is an extremely rare tumor most frequently occurring in the face or capillitium. It is felt to be an eccrine carcinoma, characterized by slow progress and unpredictable locally infiltrative growth. Therefore micrographic surgery is important to avoid local recurrence.