A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers

Transfus Med Rev. 2018 Apr;32(2):102-110. doi: 10.1016/j.tmrv.2017.09.001. Epub 2017 Sep 19.

Abstract

The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC-encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group 1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the labeled RBCs were followed over time in vivo. The PK phase evaluated dose levels of 2.5-5 mg (Group 1B) and 15-20 mg (Group 2B) DSP encapsulated in RBCs infused into healthy randomized subjects. The mean ± SD 24-hour RBC recovery was 77.9% ± 3.3% and 72.7% ± 10.5% for Groups 1A and 2A, respectively. The mean ± SD RBC life span was 84.3 ± 8.3 days in Group 1A and 88.9 ± 6.2 days in Group 2A. The PK phase actual DSP loading doses (mean ± SEM) were 4.2 ± 0.27 mg and 16.9 ± 0.90 mg in Groups 1B and 2B, respectively. Release of dexamethasone from RBCs in vivo peaked at 1 hour, and a sustained release of dexamethasone could be detected until 35 days after the single intravenous infusion in Group 2B. The mean RBC in vivo recovery for DSP-loaded processed cells compares similarly to the 24-hour recovery of regulated RBC products intended for transfusion. There was a minimal but acceptable adverse impact on the survival of EDS-processed RBCs. DSP-loaded autologous RBCs, prepared using the EDS, delivered a sustained dose of dexamethasone in vivo.

Keywords: Ataxia telangiectasia; Dexamethasone sodium phosphate; Encapsulated; Erythrocyte.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Preservation
  • Cell Survival
  • Dexamethasone / analogs & derivatives*
  • Dexamethasone / pharmacokinetics
  • Drug Delivery Systems*
  • Erythrocyte Transfusion
  • Erythrocytes / drug effects*
  • Female
  • Healthy Volunteers
  • Hemoglobins / analysis
  • Humans
  • Male
  • Middle Aged
  • Time Factors
  • Young Adult

Substances

  • Hemoglobins
  • dexamethasone 21-phosphate
  • Dexamethasone