A new ex vivo method to assess the local pharmacokinetic after tacrolimus eluting stent deployment in rat aorta

This work aimed to develop an ex vivo method able to discriminate the drug eluting stent formulative variables which can modulate in vivo local pharmacokinetic using explanted rat aorta. The apparatus, made of water-jacked tissue baths filled with Krebs-Henseleit buffer, peristaltic pump and fraction collector, assured the aorta contractile function over 5 days. The set-up was defined by using four types of tacrolimus eluting stent, having different in vitro drug release rate constants and ability to modulate in vivo tacrolimus concentration in the rabbit iliac artery. The method enabled us to determine tacrolimus arterial loading and transmural diffusion. Arterial loading overlapped with in vivo data. Only a slight overestimation of the tacrolimus amount eluted from the stents was registered suggesting that transmural diffusion was probably affected by the removal of tissues surrounding the vessel. The data also highlighted the enhancing effect of ascorbyl palmitate, one of the excipient used in tacrolimus eluting stent formulation, on arterial loading which was attributed to the increase of the tacrolimus solubility at the stent/artery wall interface.