Distribution of ~3HDexamethasone in Rat Subcutaneous Tissue after Delivery from Osmotic Pumps

摘要

Inflammation surrounding implantable glucose sensors may be controlled through local release of dexamethasone at the site of implantation.In the present study,we evaluated the distribution of dexamethasone in rat subcutaneous tissue during the first 2.5 days after local release.Osmotic pumps containing ~3Hdexamethasone were implanted into the subcutaneous tissue of rats.Digital autoradiography was used to measure the distribution of the ~3Hdexamethasone within the subcutaneous tissue at 6,24,and 60 h after implantation.Measured concentration profiles,near the catheter tip through which the agent was released,were compared to mathematical models of drug diffusion and elimination.The results demonstrate that the majority of the ~3H-dexamethasone delivered into the subcutaneous tissue was found within a 3 mm region surrounding the catheter tip.There was good agreement between the experimental data and the mathematical model.The diffusion coefficient for dexamethasone in subcutaneous tissue was found to be D =4.11 +-1.77 x 10~(-10)m~2/s,and the elimination rate constant was found to be k =3.65 +-2.24 x 10~(-5)s~1.The diffusion coefficient and elimination rate constants for dexamethasone in subcutaneous tissue have not been previously reported.The use of a mathematical model may be useful in predicting the effectiveness of local delivery of dexamethasone around implantable glucose sensors.