Am J Perinatol 1999; 16(1): 1-6
DOI: 10.1055/s-2007-993827
ORIGINAL ARTICLE

© 1999 by Thieme Medical Publishers, Inc.

Pharmacokinetics of Endobronchial Tolazoline Administration in Dogs

Gideon Paret1 , Ori Eyal1 , Haim Mayan2 , Ron Ben-Abraham1 , Amir Vardi1 , Yossi Manisterski1 , Zohar Barzilay1 , David Ezra2
  • 1Department of Pediatric Intensive Care, The Chaim Sheba Medical Center, Tel Hashomer, affiliated to The Sackler School of Medicine, Tel Aviv University, Israel
  • 2Division of Clinical Pharmacology, The Chaim Sheba Medical Center, Tel Hashomer, affiliated to The Sackler School of Medicine, Tel Aviv University, Israel
Further Information

Publication History

Publication Date:
04 March 2008 (online)

ABSTRACT

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 μg ·mL-1 The volume of distribution was 1657 ± 321 mL ·kg-1 after 12.4 ± 16.6 min. The extent of tolazoline absorption was 319 ± 38 μg ·min-1 mL-1. The total body clearance was 10.9 ± 4.8 mL ·min-1 ·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.