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Optimal prophylactic dosage and disposition of micafungin in living donor liver recipients

Satoshi Kishino1, Keiko Ohno, Tsuyoshi Shimamura

  • 1Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Tokyo, Japan. skishino@my-pharm.ac.jp

Clinical Transplantation
|November 2, 2004
PubMed

Insights

Micafungin effectively prevents fungal infections in liver transplant patients. A daily dose of 40-50 mg achieves therapeutic levels, with minimal impact from continuous venovenous hemodialysis (CVVH).

Area of Science:

  • Pharmacology
  • Transplantation Medicine
  • Infectious Diseases

Background:

  • Micafungin is a novel echinocandin antifungal with a favorable safety profile and efficacy against Candida and Aspergillus species.
  • Optimal prophylactic dosing and pharmacokinetic disposition of micafungin in liver transplant recipients remain under-investigated.
  • The impact of continuous venovenous hemodialysis (CVVH) on micafungin pharmacokinetics requires clarification.

Purpose of the Study:

  • To determine the optimal prophylactic dosage of micafungin in liver transplant recipients.
  • To investigate the pharmacokinetic disposition of micafungin in this patient population.
  • To evaluate the effect of CVVH on micafungin pharmacokinetics.

Main Methods:

  • A pharmacokinetic study involving six living donor liver transplant patients.
  • Plasma concentrations (Cmax, Cmin, AUC 0-12h, t1/2) of micafungin were measured.
  • Micafungin concentrations were assessed at the inlet and outlet of the dialyzer during CVVH.

Main Results:

  • Mean Cmax was 6.31 ± 1.08 µg/mL, Cmin was 1.65 ± 0.54 µg/mL, t1/2 was 13.63 ± 2.77 h, and AUC 0-12h was 50.04 ± 6.48 µg·h/mL.
  • Micafungin concentrations at the dialyzer inlet and outlet were similar (ratio 0.96 ± 0.04), with low clearance (0.054 ± 0.04 mL/min/kg) and minimal ultrafiltrate loss (1.0 mg).
  • A daily micafungin dosage of 40-50 mg achieved therapeutic drug levels without significant pharmacokinetic alterations during CVVH.

Conclusions:

  • Micafungin is effective in preventing systemic fungal infections post-liver transplantation.
  • A daily dose of 40-50 mg micafungin is recommended for liver transplant recipients to achieve therapeutic levels.
  • CVVH has a negligible effect on micafungin pharmacokinetics, obviating the need for dose adjustments.

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