Software for Dosage Individualization of Voriconazole: a Prospective Clinical Study.

Voriconazole is a first-line antifungal agent. Therapeutic drug monitoring is a standard of care. The best way to adjust dosages to achieve desired drug exposure endpoints is unclear due to nonlinear and variable pharmacokinetics.

Repurposing and Reformulation of the Antiparasitic Agent Flubendazole for Treatment of Cryptococcal Meningoencephalitis, a Neglected Fungal Disease.

Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply, and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum antiparasitic activity but also have antifungal activity that includes Flubendazole (a benzimidazole) has been reformulated by Janssen Pharmaceutica as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis.

Ethambutol Partitioning in Tuberculous Pulmonary Lesions Explains Its Clinical Efficacy.

Clinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against nongrowing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value.

Experimental Models of Short Courses of Liposomal Amphotericin B for Induction Therapy for Cryptococcal Meningitis.

Cryptococcal meningoencephalitis is a rapidly lethal infection in immunocompromised patients. Induction regimens are usually administered for 2 weeks. The shortest effective period of induction therapy with liposomal amphotericin B (LAMB) is unknown.

Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children.

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD.

Vancomycin toxicity in neonates: a review of the evidence.

Purpose Of Review: Vancomycin is a first-line agent in the treatment of serious Gram-positive infections in the neonatal population. The published evidence on vancomycin toxicity in neonates is limited. This review summarizes preclinical studies and clinical trials describing vancomycin toxicity.

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology.

Itraconazole: an update on pharmacology and clinical use for treatment of invasive and allergic fungal infections.

Introduction: Fungal infections are a major source of global morbidity and mortality. Itraconazole is a triazole antifungal agent that is widely used for the prevention and treatment of fungal infection. While newer antifungal agents are now available, itraconazole is an orally bioavailable agent with broad-spectrum antifungal activity.

Antifungal agents and therapy for infants and children with invasive fungal infections: a pharmacological perspective.

Invasive fungal infections, although relatively rare, are life-threatening diseases in premature infants and immunocompromised children. While many advances have been made in antifungal therapeutics in the last two decades, knowledge of the pharmacokinetics and pharmacodynamics of antifungal agents for infants and children remains incomplete. This review summarizes the pharmacology and clinical utility of currently available antifungal agents and discusses the opportunities and challenges for future research.

Delineating the 17q24.2-q24.3 microdeletion syndrome phenotype.

We present an 11-year-old girl with a 2.3 Mb de novo interstitial deletion in chromosome 17q24.2-q24.

Pharmacokinetics and pharmacodynamics of posaconazole for invasive pulmonary aspergillosis: clinical implications for antifungal therapy.

Background: Posaconazole is a triazole with anti-Aspergillus activity. However, little is known about the utility of posaconazole as primary therapy for invasive pulmonary aspergillosis.

Methods: An in vitro model of the human alveolus was used to study the impact of minimum inhibitory concentrations (MIC) on exposure-response relationships.

Pharmacokinetics and pharmacodynamics of amphotericin B deoxycholate, liposomal amphotericin B, and amphotericin B lipid complex in an in vitro model of invasive pulmonary aspergillosis.

The pharmacodynamic and pharmacokinetic (PK-PD) properties of amphotericin B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of amphotericin B deoxycholate (DAmB), liposomal amphotericin B (LAmB) and amphotericin B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated.

Tremor: a newly described adverse event with long-term itraconazole therapy.

Itraconazole is a widely prescribed triazole antifungal drug, often given for long periods. The authors report five cases of tremor related to itraconazole therapy, which occurred within 1-12 months of initiating treatment and resolved gradually following itraconazole withdrawal.

Toxicodynamics of itraconazole: implications for therapeutic drug monitoring.

We explored concentration-toxicity relationships for itraconazole among 216 patients. Logistic regression revealed a progressive increase in the probability of toxicity with increasing concentrations of itraconazole. Classification and regression tree analysis suggested that 17.