Considerations of Micafungin Regimen for Candida and Aspergillus Infections Based on Pharmacokinetic-Pharmacodynamic Target Attainment Analysis

K. IKAWA1, K. NOMURA 2, N. MORIKAWA 1, K. IKEDA 1, M. TANIWAKI 2

Author address: 

1Hiroshima Univ., Hiroshima, Japan, 2Kyoto Prefectural Univ. of Med., Kyoto, Japan.

Abstract: 

Background: A pharmacokinetic-pharmacodynamic (PK-PD) target attainment analysis has not yet assessed micafungin regimens for both Candida and Aspergillus infections. Methods: Plasma drug concentrations (48 samples from 10 adult patients) were analyzed by population pharmacokinetic modeling using NONMEM and used for a Monte Carlo simulation with MIC data to evaluate the ability of regimens to attain genus-dependent PK-PD targets, namely fungistatic and fungicidal targets against Candida spp. (area under the plasma unbound (1%) drug concentration-time curve over 24 h/MIC (fAUC/MIC) = 10 and 20) and an effective concentration target against Aspergillus spp. (plasma unbound drug concentration over 24 h = 0.05 mg/L). Results: Mean (variance) values for two-compartment pharmacokinetic model parameters were: clearance, 0.762 L/h (15.4%); volume of central compartment, 9.25 L (24.6%); intercompartmental clearance, 7.02 L/h (fixed); volume of peripheral compartment, 8.86 L (71.8%). The Monte Carlo simulation demonstrated that 50 mg q24h and 150 mg q24h for the fungistatic and fungicidal targets achieved a >95% target attainment probability against Candida spp. (Table). To achieve such probability against Aspergillus spp., 250 mg q24h or 100 mg q12h was required. Conclusions: The results rationalize the FDA-approved micafungin dosages for Candida infections (50 mg q24h for prophylaxis and 150 mg q24h for treatment). For Aspergillus infections, a regimen of 200-250 mg/day should be initiated to ensure the highest likelihood of a favorable outcome and the regimen can be optimized by decreasing dosing interval.
2009

abstract No: 

A1-582

Full conference title: 

49th Annual ICAAC
    • ICAAC 49th