Evaluating the efficacy of subcutaneous C1-esterase inhibitor administration for use in rat models of inflammatory diseases.
Autor: | Emmens RW; Department of Pathology ., Naaijkens BA, Roem D, Kramer K, Wouters D, Zeerleder S, van Ham MS, Niessen HW, Krijnen PA |
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Jazyk: | angličtina |
Zdroj: | Drug delivery [Drug Deliv] 2014 Jun; Vol. 21 (4), pp. 302-6. Date of Electronic Publication: 2013 Nov 12. |
DOI: | 10.3109/10717544.2013.853211 |
Abstrakt: | Context: 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. Materials and 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. Conclusion: These combined results indicate that in rats, subcutaneous injections in the present formulation are not effective as alternative administration route for C1-inh. |
Databáze: | MEDLINE |
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