Background: Micafungin is an echinocandin that has been used in neonates and children. We developed three pediatric population PK models for micafungin. Methods: Micafungin was administered over 0.5 and 1 hour in neonates (n=22) and children (n=72), respectively. Serum concentrations were determined by HPLC. Samples were obtained on day 1 and at steady state in the majority of patients. Data were modeled using the nonparameteric adaptive grid program with adaptive γ and weighted using the inverse of the estimated assay variance. The relationships between the individual Bayesian parameter estimates and relevant covariates were studied. Results: The mean Â± SD weight and postconceptional age in neonates was 1.37 Â± 0.39 kg and 31.14 Â± 3.26 weeks, respectively. The weight and age in children was 35.65 Â± 18.66 kg and 9.01 Â± 4.47 years, respectively. The population PK parameters in neonates were: Vc 0.34 Â± 0.11 L, Kcp 3.42 Â± 5.72 h-1, Kpc 2.63 Â± 6.12 h-1, clearance 0.077 Â± 0.065 L/h; r2 98.5%; mean weighted error (MWE) -0.74, bias adjusted mean weighted squared error (BMWSE) 26.18. The population PK parameters in children were: Vc 5.85 Â± 3.42 L, Kcp 0.97 Â± 2.04 h-1, Kpc 1.54 Â± 4.03 h-1, clearance 0.64 Â± 0.36 L/h; r2 95.9%, MWE -0.93, BMWSE 22.2. In children, there was a linear relationship between clearance and weight. An expanded model incorporating weight produced a significantly more likely solution (p=0.013) and revealed: Vc 5.18 Â± 2.75 L, Kcp 1.85 Â± 4.23 h-1, Kpc 2.39 Â± 6.37 h-1, clearance = (A + Bx weight), where A=0.48 Â± 0.21 L/h and B=0.0034 Â± 0.0045 L/h/kg; r2 95.9%, MWE -0.49, BMWSE 23.23. For all three models, the parameter means and dispersions could be recapitulated using Monte Carlo simulation. Conclusions: Pediatric population PK models for micafungin have been developed and will aid in a further understanding of the prophylactic and therapeutic role of this agent.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th