TY - JOUR
T1 - Influence of serum and albumin on echinocandin in vitro potency and pharmacodynamics
AU - Nasar, Aasya
AU - Ryan, Laurajo
AU - Frei, Christopher R.
AU - Cota, Jason M.
AU - Wiederhold, Nathan P.
N1 - Funding Information:
Conflict of Interest A. Nasar: none; L. Ryan: none; C.R. Frei: supported by an NIH/KL2 career development award (RR025766) during the time this work was performed. In addition, C.R.F. has received research grants from AstraZeneca, Bristol Myers Squibb, Elan, Ortho-McNeil Janssen, and Pfizer and has served as a scientific consultant/advisor for Forest and Ortho-McNeil Janssen; J.M. Cota: none; N.P. Wiederhold: received research support from Pfizer, Schering-Plough, Merck, Basilea, and Astellas, and has advisory boards for Merck, Astellas, Toyama, and Viamet.
PY - 2013/6
Y1 - 2013/6
N2 - The echinocandins target fungi by inhibiting the production of (1,3)-β-d-glucan, an essential component of the fungal cell wall. These agents have less toxicity to mammalian cells, as compared to other antifungals; however, they maintain potent activity against many pathogenic fungi, including polyene- and azole-resistant isolates. Members of this class are highly protein-bound, and the addition of serum or albumin to the growth medium has profound effects on their in vitro potency and pharmacodynamics. In addition, studies have demonstrated an association between in vitro activity, in the presence of serum, and outcomes in animal models of invasive fungal infections. Serum and albumin may also be useful to help detect echinocandin-resistant Candida isolates with point mutations in the gene that encodes for glucan synthase. Thus, in vitro studies evaluating echinocandins in the presence of protein can provide valuable insight regarding their potency and pharmacodynamics.
AB - The echinocandins target fungi by inhibiting the production of (1,3)-β-d-glucan, an essential component of the fungal cell wall. These agents have less toxicity to mammalian cells, as compared to other antifungals; however, they maintain potent activity against many pathogenic fungi, including polyene- and azole-resistant isolates. Members of this class are highly protein-bound, and the addition of serum or albumin to the growth medium has profound effects on their in vitro potency and pharmacodynamics. In addition, studies have demonstrated an association between in vitro activity, in the presence of serum, and outcomes in animal models of invasive fungal infections. Serum and albumin may also be useful to help detect echinocandin-resistant Candida isolates with point mutations in the gene that encodes for glucan synthase. Thus, in vitro studies evaluating echinocandins in the presence of protein can provide valuable insight regarding their potency and pharmacodynamics.
KW - Albumin
KW - Anidulafungin
KW - Caspofungin
KW - Echinocandins
KW - Micafungin
KW - Protein binding
KW - Serum
UR - https://www.scopus.com/pages/publications/84882861743
UR - https://www.scopus.com/pages/publications/84882861743#tab=citedBy
U2 - 10.1007/s12281-013-0136-z
DO - 10.1007/s12281-013-0136-z
M3 - Article
AN - SCOPUS:84882861743
SN - 1936-3761
VL - 7
SP - 89
EP - 95
JO - Current Fungal Infection Reports
JF - Current Fungal Infection Reports
IS - 2
ER -