Population Pharmacokinetics of Micafungin in Neonates and Young Infants

Antimicrobial Agents and Chemotherapy
2010.0

Abstract

Micafungin is an echinocandin with potent activity against Candida spp. Hematogenous Candida meningoencephalitis (HCME) is a frequent complication of disseminated Candida infection in premature infants. A preclinical model of HCME suggests that micafungin may be an effective agent for this syndrome, but relatively high weight-based dosages are required. This prompted the further study of the safety and pharmacokinetics (PK) of micafungin in infants. Here, we describe the population pharmacokinetics of micafungin in 47 infants with a proven or presumptive diagnosis of disseminated candidiasis, who received 0.75, 1.5, 3, 7, 10, and 15 mg/kg of micafungin. The drug was infused daily, and samples were taken in the first dosing interval and at steady state. Serum concentrations were measured using high-performance liquid chromatography (HPLC). Data were modeled using an allometric pharmacokinetic model using a three-fourths scaling exponent for clearance and parameters normalized to a 70-kg adult. Drug exposures were estimated using Monte Carlo simulation. Optimal sampling times were determined using D-optimal design theory. The fit of the allometric model to the data was highly acceptable. The pharmacokinetics of micafungin were linear. The weight-normalized estimates of clearance and volume of distribution approximated those previously described for adults. The original population parameter values could be recapitulated in the Monte Carlo simulations. A dosage of 10 mg/kg/day resulted in 82.6% of patients with areas under the concentration-time curve (AUCs) that are associated with near-maximal decline in fungal burden within the central nervous system (CNS).

Knowledge Graph

Similar Paper

Population Pharmacokinetics of Micafungin in Neonates and Young Infants
Antimicrobial Agents and Chemotherapy 2010.0
In Vivo Pharmacodynamic Target Investigation for Micafungin against Candida albicans and C. glabrata in a Neutropenic Murine Candidiasis Model
Antimicrobial Agents and Chemotherapy 2008.0
Once-Weekly Micafungin Therapy Is as Effective as Daily Therapy for Disseminated Candidiasis in Mice with Persistent Neutropenia
Antimicrobial Agents and Chemotherapy 2007.0
Intrapulmonary Pharmacokinetics and Pharmacodynamics of Micafungin in Adult Lung Transplant Patients
Antimicrobial Agents and Chemotherapy 2010.0
In Vivo Comparison of the Pharmacodynamic Targets for Echinocandin Drugs against Candida Species
Antimicrobial Agents and Chemotherapy 2010.0
Micafungin Concentrations from Brain Tissue and Pancreatic Pseudocyst Fluid
Antimicrobial Agents and Chemotherapy 2010.0
Pharmacokinetics of Penicillin G in Infants with a Gestational Age of Less than 32 Weeks
Antimicrobial Agents and Chemotherapy 2007.0
Bronchopulmonary Disposition of Micafungin in Healthy Adult Volunteers
Antimicrobial Agents and Chemotherapy 2009.0
Systematic Comparison of the Population Pharmacokinetics and Pharmacodynamics of Piperacillin in Cystic Fibrosis Patients and Healthy Volunteers
Antimicrobial Agents and Chemotherapy 2007.0
Pharmacokinetics of Aztreonam in Healthy Subjects and Patients with Cystic Fibrosis and Evaluation of Dose-Exposure Relationships Using Monte Carlo Simulation
Antimicrobial Agents and Chemotherapy 2007.0