TY - JOUR
T1 - Discomfort from an alkaline formulation delivered subcutaneously in humans
T2 - Albumin at pH 7 versus pH 10
AU - Ward, W. Kenneth
AU - Castle, Jessica R.
AU - Branigan, Deborah L.
AU - Massoud, Ryan G.
AU - El Youssef, Joseph
N1 - Funding Information:
We are grateful to the research subjects and to the Juvenile Diabetes Research Foundation and the Legacy Good Samaritan Foundation for financial support. With regard to potential conflicts of interest, a patent has been submitted by the authors for the use of glucagon formulated at alkaline pH in persons with diabetes.
PY - 2012
Y1 - 2012
N2 - 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 sixpoint 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.
AB - 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 sixpoint 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.
KW - Albumin-human
KW - Injection-site-pain
KW - Subcutaneous.
UR - http://www.scopus.com/inward/record.url?scp=84862020539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862020539&partnerID=8YFLogxK
U2 - 10.2165/11632840-000000000-00000
DO - 10.2165/11632840-000000000-00000
M3 - Article
C2 - 22568666
AN - SCOPUS:84862020539
SN - 1173-2563
VL - 32
SP - 433
EP - 438
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 7
ER -