A. Baumbach et al., Local drug delivery: Impact of pressure, substance characteristics, and stenting on drug transfer into the arterial wall, CATHET C IN, 47(1), 1999, pp. 102-106
Injection parameters for local drug delivery are frequently determined by s
tudies with marker substances. However, the pharmacologic properties of the
actual drug may influence delivery efficiency and lead to different result
s. Aim of this study was to assess the delivery capacities of two device-dr
ug combinations in order to verify this approach for further in vivo studie
s, Tritiated (H-3) preparations (5 ml) of the hydrophylic low-molecular-wei
ght heparin reviparin and the lipophilic taxane paclitaxel were injected in
to the left anterior descending artery of freshly explanted porcine hearts
with the Infusasleeve II catheter system. A balloon support pressure of 6 a
tm and infusion pressures of 40, 60, 80, or 100 psi were used. In three add
itional groups, reviparin was injected following stent implantation and pac
litaxel was injected prior to or following stent implantation, Arteries alo
ng with surrounding myocardium were harvested. The artery was carefully dis
sected, and artery and myocardium were separately homogenized, and activity
was measured. Of the totally delivered activity, 0.09% +/- 0.03% (40 psi)
to 0.17% +/- 0.13% (100 psi) of reviparin and 2.03% +/- 0.67% (60 psi) to 2
.68% +/- 1.57% (100 psi) of paclitaxel were found in the vessel wall, The r
esults for different injection pressures were not significantly different f
or either drug. The percentage activity delivered to the vessel wall was su
bstantially larger in the paclitaxel group as compared to reviparin deliver
y (P < 0.01 at 60, 80, and 100 psi), The mean concentration of reviparin in
the artery was 20 to 33 times higher than in the myocardium. For paclitaxe
l the factors were 110 to 243, Stent implantation prior to or following loc
al delivery did not result in a different delivery efficiency. The results
demonstrate that the characteristics of the delivered drug contribute large
ly to the delivery efficiency. Using identical injection parameters, drug c
oncentrations in the arterial wall were significantly higher for the lipoph
ilic paclitaxel as compared to the hydrophilic reviparin. Stenting of the a
rtery did not influence delivery efficiency. Cathet. Cardiovasc. Intervent.
47:102-106, 1999. (C) 1999 Wiley-Liss, Inc.