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Endotracheal tolazoline: Pharmacokinetics and pharmacodynamics in dogs
Year:
1999
Authors :
עזרא, דוד
;
.
Volume :
88
Co-Authors:
Paret, G., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Eyal, O., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Mayan, H., Division of Clinical Pharmacology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Gilad, E., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Ben-Abraham, R., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Ezra, D., Division of Clinical Pharmacology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Barzilay, Z., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Facilitators :
From page:
1020
To page:
1023
(
Total pages:
4
)
Abstract:
Tolazoline is a potent vasodilator of both 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 of the newborn (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endotracheal tolazoline in order to determine the relationship between endotracheal tolazoline administration, plasma concentration and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endotracheally to 7 newborn dogs, and its serum concentration and the haemodynamic parameters were monitored for 270 min post-delivery. Results are expressed as median and quartiles. It was found that 15 s after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 2.64 (1.36;13.16) μg/ml. The extent of tolazoline absorption was 305 (148;453) μg/min/ml. The volume of distribution was 3.4 (1.6;7.4) I/kg. The total body clearance was 12.1 (10.9;23.9) ml/min/kg and the elimination half-life was 225 (171;303) min. Endotracheal tolazoline produced an initial short-lived decrease in mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endotracheal tolazoline significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. A single endotracheal dose of tolazoline is effectively absorbed and produces measurable pharmacological effects. Determining the optimal endotracheal dose of tolazoline in the clinical setting requires additional evaluation.
Note:
Related Files :
animal experiment
Animals
Dogs
drug absorption
drug elimination
Female
Hemodynamic Processes
Male
עוד תגיות
תוכן קשור
More details
DOI :
10.1080/08035259950168559
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
23793
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:02
Scientific Publication
Endotracheal tolazoline: Pharmacokinetics and pharmacodynamics in dogs
88
Paret, G., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Eyal, O., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Mayan, H., Division of Clinical Pharmacology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Gilad, E., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Ben-Abraham, R., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Ezra, D., Division of Clinical Pharmacology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Barzilay, Z., Dept. of Pediatric Intensive Care, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Endotracheal tolazoline: Pharmacokinetics and pharmacodynamics in dogs
Tolazoline is a potent vasodilator of both 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 of the newborn (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endotracheal tolazoline in order to determine the relationship between endotracheal tolazoline administration, plasma concentration and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endotracheally to 7 newborn dogs, and its serum concentration and the haemodynamic parameters were monitored for 270 min post-delivery. Results are expressed as median and quartiles. It was found that 15 s after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 2.64 (1.36;13.16) μg/ml. The extent of tolazoline absorption was 305 (148;453) μg/min/ml. The volume of distribution was 3.4 (1.6;7.4) I/kg. The total body clearance was 12.1 (10.9;23.9) ml/min/kg and the elimination half-life was 225 (171;303) min. Endotracheal tolazoline produced an initial short-lived decrease in mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endotracheal tolazoline significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. A single endotracheal dose of tolazoline is effectively absorbed and produces measurable pharmacological effects. Determining the optimal endotracheal dose of tolazoline in the clinical setting requires additional evaluation.
Scientific Publication
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