Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation

Oshima, Kiyohiro; Kanda, Yoshinobu; Kako, Shinichi; Ohno, Keiko; Kishino, Satoshi; Kurokawa, Mineo

doi:10.1111/tid.12070

Cited by 8 publications

(7 citation statements)

References 12 publications

(16 reference statements)

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“…(especially C. glabrata) were mostly not detected in the MICF bottles before the concentrations were reduced to 6.25% to 12.5% of the C max . Since the minimum serum concentrations with the standard echinocandin therapy are usually within a range of 1 to 6 mg/liter (13,24,25), i.e., about 10 to 50% of the C max of the agent, detection is not reliable even when the cultures are collected shortly before serum trough levels of the echinocandins are expected.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents

et al. 2013

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Clinical practice guidelines recommend performing follow-up cultures for patients with candidemia in order to determine the time when Candida is cleared from the bloodstream. Since this requires culturing blood samples from patients undergoing antifungal treatment, we evaluated two blood culture bottles (the Bactec Mycosis IC/F [MICF], specifically adapted to the growth of fungi, and the Bactec Plus Aerobic/F [PAF], containing resins to inactivate anti-infective agents) for their effectiveness in detecting Candida albicans and Candida glabrata when seeded in concentrations of 1 CFU/ml and 10 CFU/ml, respectively, together with human whole blood and various antifungal agents in therapeutic peak serum concentrations (C max ). Significant differences between the MICF and PAF vials for the detection of Candida spp. were found when inoculated with caspofungin (0/12 versus 8/12) (P < 0.001) or amphotericin B (3/12 versus 12/12) (P < 0.001). Inoculation of fluconazole or voriconazole did not influence the effectiveness of detection in the MICF and PAF bottles (P ‫؍‬ 1.0). Neither the MICF nor the PAF bottles detected Candida spp. reliably when seeded together with anidulafungin (1/12 versus 1/12) (P ‫؍‬ 1.0) or micafungin (0/12 versus 1/12) (P ‫؍‬ 1.0). The times to positivity of both bottles were significantly prolonged when antifungal agents were added compared to those of controls without antimycotic drugs (P < 0.001). Overall, the results of this in vitro study indicate that the PAF bottles detected Candida spp. more reliably than the MICF bottles when supplemented with certain antifungal agents. Consequently, clinical studies should evaluate whether this holds true when blood cultures from patients undergoing antifungal treatment are performed.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents

et al. 2013

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“…When serum bilirubin concentration was >5 mg/dL and/or serum γ-glutamyltransferase level was >500 IU/L, median C min was 10.5 and C max was 27.6 µg/mL. In patients with lower bilirubin and γ-glutamyltransferase, the values amounted to 4.8 and 15.8 µg/mL, respectively [ 366 ]. Thus, the effect of impaired liver function on micafungin pharmacokinetics appears to be variably and hardly predictable.…”

Section: Micafunginmentioning

confidence: 99%

Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients

2017

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IntroductionBecause of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety.Materials and methodsThis review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy.Conclusions and discussionAmphotericin B is eliminated unchanged via urine and faeces. Flucytosine and fluconazole display low protein binding and are eliminated by the kidney. Itraconazole, voriconazole, posaconazole and isavuconazole are metabolised in the liver. Azoles are substrates and inhibitors of cytochrome P450 (CYP) isoenzymes and are therefore involved in numerous drug–drug interactions. Anidulafungin is spontaneously degraded in the plasma. Caspofungin and micafungin undergo enzymatic metabolism in the liver, which is independent of CYP. Although several drug–drug interactions occur during caspofungin and micafungin treatment, echinocandins display a lower potential for drug–drug interactions. Flucytosine and azoles penetrate into most of relevant tissues. Amphotericin B accumulates in the liver and in the spleen. Its concentrations in lung and kidney are intermediate and relatively low myocardium and brain. Tissue distribution of echinocandins is similar to that of amphotericin. Combination antifungal therapy is established for cryptococcosis but controversial in other IFIs such as invasive aspergillosis and mucormycosis.

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“…PK of micafungin in patients with hematological diseases are comparable with those in healthy volunteers [44,47], although acute and chronic graft-versus-host disease with liver involvement and consequent hepatic impairment significantly influenced micafungin C max and C min (increases of 175 and 218%, respectively) [119].…”

Section: Micafunginmentioning

confidence: 99%

Impact of special patient populations on the pharmacokinetics of echinocandins

Muilwijk¹,

Lempers²,

Burger³

et al. 2015

Expert Review of Anti-infective Therapy

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Echinocandins belong to the class of antifungal agents. Currently, three echinocandin drugs are licensed for intravenous treatment of invasive fungal infections: anidulafungin, caspofungin and micafungin. While their antifungal activity overlaps, there are substantial differences in pharmacokinetics (PK). Numerous factors may account for variability in PK of echinocandins including age (pediatrics vs adults), body surface area and body composition (normal weight vs obesity), disease status (e.g., critically ill and burn patients) and organ dysfunction (kidney and liver impairment). Subsequent effects of altered exposure might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal clinical utilization of echinocandin in a specific patient or patient population. This review provides up-to-date information on PK data of anidulafungin, caspofungin and micafungin in special patient populations. Patient populations addressed are neonates, children and adolescents, obese patients, patients with hepatic or renal impairment, critically ill patients (including burn patients) and patients with hematological diseases.

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Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation

Abstract: These findings suggest that the pharmacokinetics of MCFG is affected only by severely impaired liver function.

Cited by 8 publications

References 12 publications

Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents

Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents

Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients

Impact of special patient populations on the pharmacokinetics of echinocandins

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