Pharmacokinetics of micafungin in patients with severe burn injuries

Introduction

Micafungin (MCFG), an echinocandin antifungal agent, exhibits more potent antifungal activity against a broad spectrum of clinically important Candida and Aspergillus species [1]. However, there are few pharmacokinetic data of antifungal agents for burned patients, and determination of the dosage for these populations requiring initially a large quantity of fluid therapy can trouble burn surgeons and intensivists. The purpose of this study is to obtain the pharmacokinetic data for MCFG in severe burned patients.

Methods

In six patients with severe burn injuries within 14 days after injuries (19 to 82 years old, 36 to 85% TBSA), we measured the plasma concentration of MCFG by high-performance liquid chromatography [2] after drip infusion of MCFG, at 200 to 300 mg/day over a 1-hour period. Blood samples were collected at the end of the initial administration of MCFG (peak value after initial administration; A point), immediately before the second dosing (trough value after initial administration; B), at the end of the fourth dosing (steady-state peak value; C), and immediately before the fifth dosing (steady-state trough value; D). The control value of plasma concentration of MCFG assumed the pharmacokinetics value obtained from healthy volunteers.

Results

The plasma concentration of MCFG at the A point were 10.1 to 24.2 μg/ml, 1.8 to 6.1 μg/ml at B, 11.3 to 27.9 μg/ml at C, and 2.3 to 7.9 μg/ml at D. In both peak and trough values there was a good correlation between the plasma concentration of MCFG and the dose of MCFG per kilogram body weight the same as cases of healthy volunteers (Figure 1).

Figure 1

Correlation between the plasma concentration of MCFG and the dose of MCFG (mg/kg).

Conclusions

These results suggest that MCFG can be administered safely to burned patients without adjusting the dose.