Evaluating the efficacy of subcutaneous C1-esterase inhibitor administration for use in rat models of inflammatory diseases.
BACKGROUND
C1-esterase inhibitor (C1-inh) therapy is currently administered to patients with C1-inh deficiency through intravenous injections. The possibility of subcutaneous administration is currently being explored since this would alleviate need for hospitalization and increase mobility and well-being of patients. Recently, it was observed in pigs that C1-inh indeed can effectively be applied by subcutaneous injection. For studies on the effectiveness of C1-inh therapy for other indications than acquired and hereditary angioedema, rats are commonly used as model animal. For rats, however, subcutaneous C1-inh administration has never been investigated.


OBJECTIVE
To evaluate the efficacy of subcutaneous C1-inh administration in rats.


METHODS
Three boli of 100 U/kg human plasma-derived C1-inh were administered to Wistar rats on three consecutive days through subcutaneous injection or intravenous injection. Blood samples were collected from the tail veins 3, 4.5 or 6 h after C1-inh administration for measurement of C1-inh plasma levels. Antigen and activity levels of C1-inh of each plasma sample were determined by means of a specific ELISA.


RESULTS
For both C1-inh antigen and C1-inh activity, 21- to 119-fold higher plasma levels were measured after intravenous administration compared with subcutaneous administration. Subcutaneous administration also resulted in C1-inh plasma levels that were less stable and with decreased relative activity.


CONCLUSIONS
These combined results indicate that in rats, subcutaneous injections in the present formulation are not effective as alternative administration route for C1-inh.
Department of Pathology .
Reindert W
RW
Emmens
Benno A
BA
Naaijkens
Dorina
D
Roem
Klaas
K
Kramer
Diana
D
Wouters
Sacha
S
Zeerleder
Marieke S
MS
van Ham
Hans W
HW
Niessen
Paul A
PA
Krijnen
D000799:Angioedema / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D050718:Complement C1 Inhibitor Protein
Cetor; in vivo; intravenous administration; pharmacokinetics; plasma levels