Intrapulmonary Pharmacokinetics and Pharmacodynamics of Micafungin in Adult Lung Transplant Patients

Abstract

Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant

Tissue Penetration of Antifungal Agents

“…micafungin dose, ELF/plasma and alveolar cell/plasma concentration ratios varied with time postdose. Mean ratios ranged from 0.1 to 1.53 at 3 h and from 1.1 to 6.2 at 24 h postdose (62). The vast majority of anidulafungin and micafungin found in the ELF is present within macrophages rather than in the fluid itself (58,61,62).…”

“…Mean ratios ranged from 0.1 to 1.53 at 3 h and from 1.1 to 6.2 at 24 h postdose (62). The vast majority of anidulafungin and micafungin found in the ELF is present within macrophages rather than in the fluid itself (58,61,62). Caspofungin, micafungin, and anidulafungin exhibit lung tissue exposures in rodents that exceed those in plasma by 1.1-fold, 2.8-fold, and 10-fold, respectively (102,103,150).…”

“…However, the concentrations of caspofungin in alveolar macrophages were Ͼ5 times the corresponding concentrations in plasma in a single patient (149). Both anidulafungin and micafungin also accumulated in the alveolar macrophages of volunteers, attaining concentrations approximately 14 and 4 times higher than those in plasma, respectively (58,62). In 18 lung transplant patients receiving a single 150-mg i.v.…”

“…For this reason, it may be more useful to present the tissue area under the concentrationtime curve (AUC) for comparison. There are few studies that do this for humans (56,57,58,59,60,61,62), and with one exception (59), all deal with pulmonary distribution. Most of the antifungal agents considered in this review do exhibit hysteresis.…”

“…Estimating concentration-time profiles (and thereby calculating the AUC in tissues) is possible using population pharmacokinetic modeling techniques. Relatively few studies have done this for humans to date (56)(57)(58)(59)(60)(61)(62), and all but one (59) deal with pulmonary distribution.…”