Trial reportBritish journal of clinical pharmacology2000
Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humans.
Trial report in British journal of clinical pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- Plasma pro-endothelin-1 peptide concentrations rise in chronic kidney disease and following selective endothelin A receptor antagonism.Journal of the American Heart Association · 2015Trial
- Efficacy and safety of atrasentan in patients with cardiovascular risk and early atherosclerosis.Hypertension (Dallas, Tex. : 1979) · 2008Trial
- Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects.British journal of clinical pharmacology · 2002Trial
- Systemic ETA receptor antagonism with BQ-123 blocks ET-1 induced forearm vasoconstriction and decreases peripheral vascular resistance in healthy men.British journal of pharmacology · 2001Trial
- Atrasentan: First Approval.Drugs · 2025Review
- Crosstalk Between Gastric Cancer and Adjacent Mucosa Reveals EDN1-EDNRA-Mediated Regulation of Cancer Stemness and Immunomodulation Networks.Journal of cellular and molecular medicine · 2025Article
- Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.Clinical and translational science · 2024Article
- Vascular actions of peripheral CGRP in migraine-like photophobia in mice.Cephalalgia : an international journal of headache · 2020Article
- Blockade of Endothelin-1 Receptor Type B Ameliorates Glucose Intolerance and Insulin Resistance in a Mouse Model of Obstructive Sleep Apnea.Frontiers in endocrinology · 2018Article
- Clinical pharmacology of an atrasentan and docetaxel regimen in men with hormone-refractory prostate cancer.Cancer chemotherapy and pharmacology · 2014Article
- Prolonged pharmacodynamic effects of S-0139, an intravenously administered endothelin A (ET) antagonist, in the human forearm blood flow model.British journal of clinical pharmacology · 2010Article
- Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model.Cancer biology & therapy · 2009Article
- Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2009Article
- Tumor-evoked sensitization of C nociceptors: a role for endothelin.Journal of neurophysiology · 2008Article
- Phase I safety study of escalating doses of atrasentan in adults with recurrent malignant glioma.Neuro-oncology · 2008Article
- Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease.Annual review of pharmacology and toxicology · 2007Review
- Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma.Cancer science · 2006Article
- Endothelin receptor A blockade enhances taxane effects in prostate cancer.Neoplasia (New York, N.Y.) · 2006Article
- Reproducibility of forearm vasodilator response to intra-arterial infusion of calcitonin gene-related peptide assessed by venous occlusion plethysmography.British journal of clinical pharmacology · 2005Article
- Endothelin receptor antagonists.World journal of urology · 2005Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsEndothelins (ETs) may play a role in the pathogenesis of a variety of cardiovascular diseases. The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT-627 in healthy humans.
methodsHealthy volunteers were included in two studies with cross-over design. Subjects received single or multiple dose (an 8 day period) administration of oralABT-627 or matched placebo, in a dose range of 0.2-40 mg. The pharmacokinetics of ABT-627 were described and its effects on systemic haemodynamics under resting conditions and on forearm vasoconstriction in response to ET-1 were assessed.
resultsABT-627 was generally well tolerated in both studies, with transient headache being the most reported adverse event (in 62% vs 4% during placebo, P < 0.05, for Study 1 and in 42% vs 60%, P = 0.2, for Study 2). ABT-627 was rapidly absorbed, reaching maximum plasma levels at approximately 1 h post dose. Single dose ABT-627, at a dose of 20 and 40 mg, inhibited ET-1 induced forearm vasoconstriction at 8 h post dose. Eight days ABT-627 treatment, at a dose level of 5 mg and above, also effectively blocked forearm vasoconstriction to ET-1. ABT-627 caused a significant reduction in peripheral resistance as compared with placebo (16 +/- 1 vs 19 +/- 1, 18 +/- 2 vs 23 +/- 3, 15 +/- 1 vs 17 +/- 1 AU at 1, 5, 20 mg in Study 2) with only a mild decrease in blood pressure (79 +/- 2 vs 84 +/- 3, 80 +/- 4 vs 90 +/- 5, 75 +/- 3 vs 79 +/- 1 at 1, 5, 20 mg in Study 2). ABT-627 caused a moderate dose-dependent increase in circulating immunoreactive ET levels (a maximal increase of 50% over baseline at the 20 mg dose level).
conclusionsThe oral ETA receptor blocker ABT-627 is well tolerated, rapidly absorbed, effectively blocks ET-1 induced vasoconstriction and causes a decrease in total peripheral resistance and mean arterial pressure. Our data suggest that ABT-627 may be a valuable tool in treatment of cardiovascular disease.
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