Pharmacokinetics and pharmacodynamics of hyaluronan infused into healthy human volunteers

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. © Hamilton et al.; Licensee Bentham Open.