Trial reportBritish journal of clinical pharmacology2002
Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects.
Trial report in British journal of clinical pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed, 39 citations in OpenAlex.
- Macitentan: entry-into-humans study with a new endothelin receptor antagonist.European journal of clinical pharmacology · 2011Trial
- Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral endothelin receptor antagonist.European journal of clinical pharmacology · 2007Trial
- Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects.British journal of clinical pharmacology · 2006Trial
- Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes.Journal of clinical medicine · 2024Article
- Current and future strategies for targeting the endothelin pathway in cardiovascular disease.Nature cardiovascular research · 2023Review
- Repurposing of the Drug Tezosentan for Cancer Therapy.Current issues in molecular biology · 2023Review
- Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond?Nephrology (Carlton, Vic.) · 2023Review
- Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system.Journal of biomedical science · 2020Article
- Target-Mediated Population Pharmacokinetic Modeling of Endothelin Receptor Antagonists.Pharmaceutical research · 2019Article
- Drugs' development in acute heart failure: what went wrong?Heart failure reviews · 2018Review
- Phase I safety study of escalating doses of atrasentan in adults with recurrent malignant glioma.Neuro-oncology · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe purpose of this study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, during chronic infusions in healthy male subjects.
methodsTezosentan was infused at a rate of 100 mg h(-1) for 6 h (study A, six subjects) and at a rate of 5 mg h(-1) for 72 h (study B, eight subjects). Both studies had a randomized, placebo-controlled, double-blind design. Tolerability and safety were monitored by the recording of vital signs, ECG, adverse events and clinical laboratory parameters. Blood samples were collected frequently for pharmacokinetic determinations and measurement of plasma endothelin-1 concentrations.
resultsIn both studies tezosentan was well tolerated with headache the most frequently reported adverse event (incidence of 75-100% for tezosentan and 50% for placebo). Plasma concentrations of tezosentan rapidly approached steady state (3000 and 125 ng ml(-1) in study A and B, respectively) and did not change upon prolonged infusion. A two-compartment model could describe its pharmacokinetic profile. The half-lives of the two disposition phases were approximately 0.10 and 3.2 h. Endothelin-1 concentrations increased rapidly 11- and 2-fold compared with pre-dose values in study A and B, respectively, during infusion of tezosentan and did not change during the 72 h infusion.
conclusionsOn the basis of these results, dose finding studies with tezosentan in acute heart failure can be initiated in the dose range 5-100 mg h(-1).
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