Perivascular tissue pharmacokinetics of dipyridamole.
OBJECTIVE
The tissue diffusivity (D(g)) and partitioning (K) for dipyridamole were determined and a model was developed to examine the relationship between perivascular dose and local dipyridamole tissue concentrations.


METHODS
Experiments were performed using an in vitro perfusion apparatus that recirculated buffer through different graft samples or normal porcine femoral arteries and veins. The grafts or blood vessels were immersed in a compartment containing Krebs-Henseleit (KH) buffer and dipyridamole (30 microg/mL). The recirculating buffer was sampled at multiple time points and dipyridamole was assayed. Estimates of the effective diffusivity (D(g)) and partition coefficient (K) of the drug in the vessel wall were determined and used to simulate dipyridamole tissue concentration after perivascular delivery.


RESULTS
Dipyridamole diffusivity within native femoral veins (D(g) = 3.87 +/- 0.93 x 10(-6) cm2/s) was approximately twice that within femoral arteries (D(g) = 2.06 +/- 0.79 x 10(-6) cm2/s, p < 0.01). Explanted grafts showed the lowest diffusivity. Partition coefficients of femoral arteries (K = 4.11 +/- 0.99) were higher than those of femoral veins (K = 2.05 +/- 0.85, p < 0.01) and explanted graft (K = 0.89 +/- 0.56, p < 0.01).


CONCLUSIONS
The results demonstrate that local drug kinetics vary greatly for different types of blood vessels and grafts. The pharmacokinetic parameters and resulting computational simulations are helpful in exploring perivascular drug delivery strategies.
Goteti
Kosalaram
K
Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, #318, Salt Lake City, Utah 84108, USA.
Masaki
Takahisa
T
Kuji
Tadashi
T
Leypoldt
John K
JK
Cheung
Alfred K
AK
Kern
Steven E
SE
D000465:Algorithms; D000818:Animals; D001693:Biological Transport, Active; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism / Q000502:physiology; D002408:Catheters, Indwelling; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D004058:Diffusion; D004176:Dipyridamole / Q000737:chemistry / Q000493:pharmacokinetics*; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D066298:In Vitro Techniques; D015233:Models, Statistical; D010477:Perfusion; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D011138:Polytetrafluoroethylene; D011817:Rabbits; D006435:Renal Dialysis
D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D011138:Polytetrafluoroethylene