Impact of special patient populations on the pharmacokinetics of echinocandins

Abstract

Echinocandins belong to the class of antifungal agents. Currently, three echinocandin drugs are licensed for intravenous treatment of invasive fungal infections: anidulafungin, caspofungin and micafungin. While their antifungal activity overlaps, there are substantial differences in pharmacokinetics (PK). Numerous factors may account for variability in PK of echinocandins including age (pediatrics vs adults), body surface area and body composition (normal weight vs obesity), disease status (e.g., critically ill and burn patients) and organ dysfunction (kidney and liver impairment). Subsequent effects of altered exposure might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal clinical utilization of echinocandin in a specific patient or patient population. This review provides up-to-date information on PK data of anidulafungin, caspofungin and micafungin in special patient populations. Patient populations addressed are neonates, children and adolescents, obese patients, patients with hepatic or renal impairment, critically ill patients (including burn patients) and patients with hematological diseases.

Cardiac Effects of Echinocandins in Endotoxemic Rats

“…Recent studies revealed that the pharmacokinetics of echinocandins in special patient populations might impact clinical efficacy and safety (6). Septic cardiomyopathy is a wellknown organ dysfunction in sepsis, which is associated with reduced left ventricular contractility (19).…”

“…Nevertheless, evidence is mounting that the pharmacokinetics of echinocandins in special patient populations prone to systemic inflammatory responses (e.g., critical ill patients, burn patients, patients with severe organ dysfunction) may impact clinical efficacy and safety (6).…”

New facets of antifungal therapy

“…23 Though caspofungin, micafungin, and anidulafungin possess similar antifungal activities, the differences in their backbone structures lead to distinct pharmacokinetics. 88 Caspofungin may affect the plasma concentration of cyclosporine A and tacrolimus. 88 However, Saner et al demonstrated that co-administration of caspofungin with either of these 2 immunosuppressants in liver transplant patients resulted in an acceptable safety profile with no hepatotoxicity.…”

“…88 Caspofungin may affect the plasma concentration of cyclosporine A and tacrolimus. 88 However, Saner et al demonstrated that co-administration of caspofungin with either of these 2 immunosuppressants in liver transplant patients resulted in an acceptable safety profile with no hepatotoxicity. 89 In addition, based on an open-label clinical trial in healthy adults, micafungin may increase exposure to amphotericin B about 30%; thus, it may not well tolerated during co-treatment in human host.…”

Drug-interactions of azole antifungals with selected immunosuppressants in transplant patients: strategies for optimal management in clinical practice

“…significantly impact exposure of immunosuppressants [38,39]. Of note, one should be aware of a pharmacodynamic interaction between amphotericin B and calcineurin inhibitors as both classes of drugs have nephrotoxic properties [40].…”