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Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding.

Publication ,  Journal Article
Yanni, SB; Smith, PB; Benjamin, DK; Augustijns, PF; Thakker, DR; Annaert, PP
Published in: Biopharm Drug Dispos
May 2011

Micafungin, a new echinocandin antifungal agent, has been used widely for the treatment of various fungal infections in human populations. Micafungin is predominantly cleared by biliary excretion and it binds extensively to plasma proteins. Micafungin body weight-adjusted clearance is higher in neonates than in adults, but the mechanisms underlying this difference are not understood. Previous work had revealed the roles of sinusoidal uptake (Na(+) -taurocholate co-transporting peptide, NTCP; organic anion transporting polypeptide, OATP) as well as canalicular efflux (bile salt export pump, BSEP; breast cancer resistance protein, BCRP) transporters in micafungin hepatobiliary elimination. In the present study, the relative protein expression of hepatic transporters was compared between liver homogenates from neonates and adults. Also, the extent of micafungin binding to serum from neonates and adults was measured in vitro. The results indicate that relative expression levels of NTCP, OATP1B1/3, BSEP, BCRP and MRP3 were similar in neonates and in adults. However, the micafungin fraction unbound (f(u) ) in neonatal serum was about 8-fold higher than in the adult serum (0.033±0.012 versus 0.004±0.001, respectively). While there was no evidence for different intrinsic hepatobiliary clearance of micafungin between neonates and adults, our data suggest that age-dependent serum protein binding of micafungin is responsible for its higher clearance in neonates compared with adults.

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Published In

Biopharm Drug Dispos

DOI

EISSN

1099-081X

Publication Date

May 2011

Volume

32

Issue

4

Start / End Page

222 / 232

Location

England

Related Subject Headings

  • Symporters
  • Protein Binding
  • Pharmacology & Pharmacy
  • Organic Anion Transporters
  • Micafungin
  • Liver
  • Lipopeptides
  • Infant, Newborn
  • Humans
  • Echinocandins
 

Citation

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Yanni, S. B., Smith, P. B., Benjamin, D. K., Augustijns, P. F., Thakker, D. R., & Annaert, P. P. (2011). Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding. Biopharm Drug Dispos, 32(4), 222–232. https://doi.org/10.1002/bdd.752
Yanni, Souzan B., P Brian Smith, Daniel K. Benjamin, Patrick F. Augustijns, Dhiren R. Thakker, and Pieter P. Annaert. “Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding.Biopharm Drug Dispos 32, no. 4 (May 2011): 222–32. https://doi.org/10.1002/bdd.752.
Yanni SB, Smith PB, Benjamin DK, Augustijns PF, Thakker DR, Annaert PP. Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding. Biopharm Drug Dispos. 2011 May;32(4):222–32.
Yanni, Souzan B., et al. “Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding.Biopharm Drug Dispos, vol. 32, no. 4, May 2011, pp. 222–32. Pubmed, doi:10.1002/bdd.752.
Yanni SB, Smith PB, Benjamin DK, Augustijns PF, Thakker DR, Annaert PP. Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding. Biopharm Drug Dispos. 2011 May;32(4):222–232.
Journal cover image

Published In

Biopharm Drug Dispos

DOI

EISSN

1099-081X

Publication Date

May 2011

Volume

32

Issue

4

Start / End Page

222 / 232

Location

England

Related Subject Headings

  • Symporters
  • Protein Binding
  • Pharmacology & Pharmacy
  • Organic Anion Transporters
  • Micafungin
  • Liver
  • Lipopeptides
  • Infant, Newborn
  • Humans
  • Echinocandins