Clinical Drug Investigation

, Volume 32, Issue 7, pp 433–438

Discomfort from an Alkaline Formulation Delivered Subcutaneously in Humans

Albumin at pH 7 versus pH 10
  • W. Kenneth Ward
  • Jessica R. Castle
  • Deborah L. Branigan
  • Ryan G. Massoud
  • Joseph El Youssef
Original Research Article

DOI: 10.2165/11632840-000000000-00000

Cite this article as:
Ward, W.K., Castle, J.R., Branigan, D.L. et al. Clin Drug Investig (2012) 32: 433. doi:10.2165/11632840-000000000-00000

Abstract

Background and Objective: There is a paucity of data regarding tolerability of alkaline drugs administered subcutaneously. The aim of this study was to assess the tolerability of alkaline preparations of human albumin delivered subcutaneously to healthy humans.

Methods: We compared the tolerability of neutral versus alkaline (pH 10) formulations of human albumin in ten volunteers. With an intent to minimize the time required to reach physiological pH after injection, the alkaline formulation was buffered with a low concentration of glycine (20 mmol/L). Each formulation was given at two rates: over 5 seconds and over 60 seconds. A six-point scale was used to assess discomfort.

Results: For slow injections, there was a significant difference between pH 7.4 and pH 10 injections (0.4±0.2 vs 1.1±0.2, mean±SEM; p = 0.025), though the degree of discomfort at pH 10 injections was only ‘mild or slight’. For fast injections, the difference between neutral and alkaline formulations was of borderline significance. Inflammation and oedema, as judged by a physician, were very minimal for all injections, irrespective of pH.

Conclusion: For subcutaneous drug administration (especially when delivered slowly), there was more discomfort associated with alkaline versus neutral formulations of albumin, though the discomfort was mild. This study suggests that there is little discomfort and inflammation resulting from subcutaneous administration of protein drugs formulated with weak buffers at alkaline pH.

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • W. Kenneth Ward
    • 1
    • 2
  • Jessica R. Castle
    • 2
  • Deborah L. Branigan
    • 1
  • Ryan G. Massoud
    • 1
  • Joseph El Youssef
    • 2
  1. 1.Legacy Health and Legacy Research InstitutePortlandUSA
  2. 2.Oregon Health and Science University (Diabetes), Mailstop OP05DCPortlandUSA

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