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Voriconazole therapeutic drug monitoring: focus on safety. 2010

Alessandro C Pasqualotto, and Melissa O Xavier, and Huander F Andreolla, and Rafael Linden
Universidade Federal do Rio Grande do Sul, Post Graduation Program in Pulmonary Sciences, Porto Alegre, Brazil.

BACKGROUND Voriconazole has been widely used for the treatment of invasive fungal diseases, particularly invasive aspergillosis. Drug-drug interactions are, however, the main drawback associated with voriconazole use, since this drug suffers from extensive hepatic metabolism. METHODS This article reviews the current literature on voriconazole therapeutic drug monitoring, with a special focus on drug safety. RESULTS An update on voriconazole metabolism, drug interactions, toxicity and the relation of these with voriconazole drug concentrations. CONCLUSIONS Therapy with voriconazole may be better guided by measuring voriconazole concentrations in the plasma.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D001189 Aryl Hydrocarbon Hydroxylases A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides. Microsomal Monooxygenases,Xenobiotic Monooxygenases,Hydroxylases, Aryl Hydrocarbon,Monooxygenases, Microsomal,Monooxygenases, Xenobiotic
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole
D016903 Drug Monitoring The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. Monitoring, Drug,Therapeutic Drug Monitoring,Drug Monitoring, Therapeutic,Monitoring, Therapeutic Drug
D019411 Clinical Laboratory Techniques Techniques used to carry out clinical investigative procedures in the diagnosis and therapy of disease. Clinical Laboratory Test,Clinical Laboratory Testing,Clinical Laboratory Diagnoses,Clinical Laboratory Testings,Clinical Laboratory Tests,Diagnoses and Laboratory Examinations,Diagnosis, Laboratory,Laboratory Diagnosis,Laboratory Examinations and Diagnoses,Laboratory Techniques, Clinical,Clinical Laboratory Technique,Diagnose, Clinical Laboratory,Laboratory Diagnoses,Laboratory Technique, Clinical,Laboratory Test, Clinical,Laboratory Testing, Clinical,Technique, Clinical Laboratory,Test, Clinical Laboratory,Testing, Clinical Laboratory

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