Properties of pramlintide and insulin upon mixing.
OBJECTIVE
The pharmacokinetics, pharmacodynamics, and safety of pramlintide and various insulin formulations in patients with type 1 diabetes mellitus (DM) when given as separate injections or mixed in the same syringe before injection were studied.


METHODS
In two randomized, open-label, placebo-controlled, five-period-crossover studies, patients with type 1 DM received preprandial injections of pramlintide, short-acting insulin, and long-acting insulin administered either by separate injections or after mixing in various combinations. Serum free insulin and plasma glucose concentrations were measured for 10 hours and plasma pramlintide concentrations for 5 hours after injection.


RESULTS
Blood samples were collected from a total of 51 patients. All treatments involving mixtures were comparable to separate injections with respect to the area under the concentration-versus-time curve (AUC) and the maximum concentration (Cmax) of serum free insulin. There were some minor differences in the AUC and Cmax of pramlintide. No injection-site reactions or other unexpected adverse events were observed.


CONCLUSIONS
Mixing pramlintide with short- or long-acting insulin in the same syringe before subcutaneous injection did not affect the pharmacodynamics of glucose or the pharmacokinetics of insulin or pramlintide in a clinically significant manner.
Weyer
Christian
C
Regulatory and Medical Information, Amylin Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Fineman
Mark S
MS
Strobel
Susan
S
Shen
Larry
L
Data
Joann
J
Kolterman
Orville G
OG
Sylvestri
Mario F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000682:Amyloid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014481:United States
D000682:Amyloid; D004338:Drug Combinations; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010919:Placebos; C105254:pramlintide