Pharmacokinetics and pharmacodynamics of hyaluronan infused into healthy human volunteers

Sara Rae Hamilton, Mandana Veiseh, Cornelia Tölg, Rommel Tirona, Jakob Richardson, Richard Brown, Mario Gonzalez, Michael Vanzieleghem, Patricia Anderson, Samuel Asculai, Françoise Winnik, Rashmin Savani, David Freeman, Leonard Luyt, James Koropatnick, Eva Ann Turley

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8 Scopus citations

Abstract

The pharmacodynamics and elimination kinetics of escalating doses (1.5-12 mg/kg) of hyaluronan (HA) infusions were studied in healthy human volunteers. Metabolic breakdown of serum HA and associated adverse events were monitored throughout the study. The HA-binding capacities of circulating CD4+ and CD8+ T lymphocytes, CD19+ B-lymphocytes and CD14+ peripheral blood monocytes (PBMC) were also quantified. Breakdown of infused HA into small fragments (<37 kDa) were not detected and adverse events related to HA infusions were infrequent and non-serious in nature. Binding of FITC-HA was greatest to CD14+ monocytes and the binding capacity of these cells for FITC-HA was significantly increased by the final HA infusion. At that time, binding to CD14+ monocytes was related to serum HA levels suggesting a close relationship between PK and PD of serum HA. Drug level analysis demonstrated a disproportional increase in the area under the serum concentration vs. time curve with increasing HA dose. The observed non-linear HA kinetics appears to result from a saturable elimination process as revealed by pharmacokinetic modeling. These results have implications for the use of injected HA for drug delivery or in imaging applications.

Original languageEnglish (US)
Pages (from-to)43-55
Number of pages13
JournalOpen Drug Metabolism Journal
Volume3
DOIs
StatePublished - Jan 1 2009

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ASJC Scopus subject areas

  • Pharmacology

Cite this

Hamilton, S. R., Veiseh, M., Tölg, C., Tirona, R., Richardson, J., Brown, R., Gonzalez, M., Vanzieleghem, M., Anderson, P., Asculai, S., Winnik, F., Savani, R., Freeman, D., Luyt, L., Koropatnick, J., & Turley, E. A. (2009). Pharmacokinetics and pharmacodynamics of hyaluronan infused into healthy human volunteers. Open Drug Metabolism Journal, 3, 43-55. https://doi.org/10.2174/1874073100903010043