Modeling behavior of protein C during and after subcutaneous administration.
Protein C is an important blood factor protein that regulates the blood coagulation process. Deficiency of protein C can lead to excessive coagulation that results in lack of tissue oxygenation, causing conditions such as deep vein thrombosis, pulmonary embolism, and stroke. Human protein C has been approved as a treatment for congenital protein C deficiency; however, the therapy requires frequent injections, due to the short residence time of the protein. Subcutaneous administration has been examined as an alternative to increase residence time and decrease injection frequency, thereby creating a more patient-friendly dosing regimen. In order to design an efficient injection or infusion protocol for subcutaneously administered proteins, it is important to accurately model the behavior (absorption, distribution, elimination) of these proteins in the body. However, several factors involved in a subcutaneous injection of the protein make modeling this behavior a challenging task. For example, absorption of the drug from the subcutaneous site into the blood stream can be variable depending on the site of injection, physical activity of the patient, etc. Furthermore, degradation of the protein can occur at the site of injection and further modify its absorption. The objective of this work was to demonstrate the utility of frequency response modeling as an alternative method to analyze the behavior of subcutaneously administered protein C. The results of our study indicate that if the dose range yielding the constant clearance of protein C is identified for the patient, models of that type, as presented in our study, can be used to adjust optimal dosing of protein C necessary to reach prescribed levels of the protein in this patient at desired time points, both specified by treatment requirements.
Chaubal
Mahesh V
MV
Dedík
Ladislav
L
Durisová
Mária
M
Bruley
Duane F
DF
D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D008954:Models, Biological; D011486:Protein C / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D020151:Protein C Deficiency / Q000097:blood / Q000188:drug therapy
D011486:Protein C