Voriconazole: Pharmacokinetics, role in therapeutic drug monitoring and clinical outcomes

In the last twenty years, the incidence of invasive fungal infections (IFI) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections and due to the increase of infection associated with travel. Moreover IFI in infants admitted to the neonatal intensive care unit are common and often fatal. Amphotericin B was for more than 40 years the gold standard for almost all IFI, but toxicity and resistance, especially of new and emerging pathogens remained important issues. Fluconazole and itraconazole have also the same disadvantage of resistance. After a long period of relative inactivity in the introduction of new antifungals, more recently a few new drugs of already existing classes have been introduced as important agents in the treatment and prevention of IFI. These represent small or large advantages and differences compared with existing available alternative therapy for deep and systemic mycoses. Voriconazole is a second-generation triazole antifungal drug, often prescribed as first-line therapy for candidemia, in non-neutropenic hosts, for invasive pulmonary aspergillosis and as prophylaxis of many systemic mycoses. In-vitro and in-vivo studies showed that voriconazole has broad-spectrum activity against most Candida species, Aspergillus species, fusariosis or scedosporiosis. Voriconazole has non-linear pharmacokinetics and, as substrate and inhibitor of cytochrome P450, it undergoes extensive hepatic metabolism that depends on age, genetic factors, and interactions with other drugs, which may lead to enhanced toxicity of the concomitant medication(s) or ineffective antifungal treatment. This book presents an update on voriconazole research, particularly its pharmacology, microbiology, toxicology, and clinical outcomes in order to optimize its use in daily clinical practice.