Tissue Distribution of Anidulafungin in Neonatal Rats
Article first published online: 6 FEB 2012
© 2012 Wiley Periodicals, Inc.
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Volume 95, Issue 1, pages 89–94, February 2012
How to Cite
Ripp, S. L., Aram, J. A., Bowman, C. J., Chmielewski, G., Conte, U., Cross, D. M., Gao, H., Lewis, E. M., Lin, J., Liu, P. and Schlamm, H. T. (2012), Tissue Distribution of Anidulafungin in Neonatal Rats. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 95: 89–94. doi: 10.1002/bdrb.20347
- Issue published online: 16 MAR 2012
- Article first published online: 6 FEB 2012
- Manuscript Accepted: 15 OCT 2011
- Manuscript Received: 2 AUG 2011
- tissue distribution;
- neonatal rats;
Anidulafungin, an echinocandin, is currently approved for treatment of fungal infections in adults. There is a high unmet medical need for treatment of fungal infections in neonatal patients, who may be at higher risk of infections involving bone, brain, and heart tissues. This in vivo preclinical study investigated anidulafungin distribution in plasma, bone, brain, and heart tissues in neonatal rats. Postnatal day (PND) 4 and PND 8 Fischer (F344/DuCrl) rats were dosed subcutaneously once with anidulafungin (10 mg/kg) or once daily for 5 days (PND 4–8). Plasma and tissue samples were collected and anidulafungin levels were measured by liquid chromatography-tandem mass spectrometry. The mean plasma Cmax and AUC0-24 values were consistent with single-dose plasma pharmacokinetics (dose normalized) reported previously for adult rats. Observed bone concentrations were similar to plasma concentrations regardless of dosing duration, with bone-to-plasma concentration ratios of approximately 1.0. Heart concentrations were higher than plasma, with heart to plasma concentration ratios of 1.3- to 1.8-fold. Brain concentrations were low after single dose, with brain-to-plasma concentration ratio of approximately 0.23, but increased to approximately 0.71 after 5 days of dosing. Tissue concentrations were nearly identical after single-dose administration in both PND 4 and PND 8 animals, indicating that anidulafungin does not appear to differentially distribute in this period in neonatal rats. In conclusion, anidulafungin distributes to bone, brain, and heart tissues of neonatal rats; such results are supportive of further investigation of efficacy against infections involving bone, brain, and heart tissues.