Tolazoline is a potent
vasodilator of arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous
tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent
pulmonary hypertension (PPHN). Endotracheally administered
tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in the systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endobronchial
tolazoline to determine the relationship between endobronchial
tolazoline administration, plasma concentration, and its effects on the cardiovascular and respiratory systems.
Tolazoline was administered endobronchially to seven dogs, and its serum concentration and the hemodynamic parameters were monitored for 270 min postdelivery. It was found that 15 sec after dosing,
tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 9.3+/-8.0 microg x mL(-1) The volume of distribution was 1657+/-321 mL x kg(-1) after 1 2.4+/-1 6.6 min. The extent of
tolazoline absorption was 319+/-38 microg x min(-1) mL(-1). The total body clearance was 10.9 +/-4.8 mL x min(-1) x Kg(-1) and the elimination half-life was 156+/-81 min. Endobronchial
tolazoline produced an initial short-lived decrease in the mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endobronchial
tolazoline a significant
tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. We conclude that an endobronchial bolus dose of
tolazoline is effectively absorbed, produces measurable pharmacological effects, and may be beneficial in the
therapy of persistent
pulmonary hypertension of the newborn.