An in-vitro comparative study of the binding of caspofungin and micafungin to plasma proteins

Keishi Yamasaki, Keiki Sakurama, Koji Nishi, Kenji Tsukigawa, Hakaru Seo, Masaki Otagiri, Kazuaki Taguchi

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: Echinocandins are widely used for the treatment of invasive fungal diseases. While they bind strongly to plasma proteins, our knowledge of this process is not sufficient to permit their pharmacokinetics and pharmacodynamics targets to be discussed. In this study, we characterized the binding of two echinocandins, caspofungin and micafungin, to plasma proteins, human serum albumin (HSA) and human α 1-acid glycoprotein (AAG). METHODS: The binding parameters, number of binding sites (n) and association constant (K) for caspofungin and micafungin to HSA and AAG were determined by equilibrium dialysis. The binding site on HSA for these echinocandins was identified by conducting inhibition experiments. KEY FINDINGS: Caspofungin was found to bind strongly to a single site on HSA (n = 1.26, K = 0.45 × 106 M-1) and AAG (n = 0.99, K = 0.29 × 106 M-1). Micafungin was found to bind more strongly to HSA (n = 1.35, K = 1.44 × 106 M-1) and AAG (n = 1.32, K = 1.16 × 106 M-1). The binding site for these drugs on HSA appears to be within subdomain IA. CONCLUSIONS: Free fraction of caspofungin and micafungin in patients may not be substantially affected due to the contribution of AAG to the overall protein binding and the binding to subdomain IA on HSA, which is different from the major drug-binding sites within subdomains IB, IIA and IIIA.

Original languageEnglish
Pages (from-to)88-93
Number of pages6
JournalJournal of Pharmacy and Pharmacology
Volume74
Issue number1
DOIs
Publication statusPublished - 2022 Jan 5

Keywords

  • caspofungin
  • echinocandins
  • human serum albumin
  • micafungin
  • protein binding
  • α 1-acid glycoprotein

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'An in-vitro comparative study of the binding of caspofungin and micafungin to plasma proteins'. Together they form a unique fingerprint.

Cite this