Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Patricia N. Sidharta ◽  
Paul L. M. van Giersbergen ◽  
Jasper Dingemanse
Keyword(s):  
Receptor Antagonist ◽  
Healthy Subjects ◽  
Multiple Dose ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Multiple Dose Study ◽  
Dose Study

scholarly journals Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects

2009 ◽  
Vol 53 (9) ◽  
pp. 3720-3725 ◽  
Author(s):  
Ann M. Ginsberg ◽  
Martino W. Laurenzi ◽  
Doris J. Rouse ◽  
Karl D. Whitney ◽  
Melvin K. Spigelman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Dose ◽  
Healthy Subjects ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Blood Levels ◽  
Drug Resistant ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study

ABSTRACT PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic Mycobacterium tuberculosis. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support the investigation of this novel compound for the treatment of tuberculosis.

Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects

1996 ◽  
Vol 60 (2) ◽  
pp. 124-137 ◽  
Author(s):  
Cornelia Weber ◽  
Rita Schmitt ◽  
Herbert Birnboeck ◽  
Gerard Hopfgartner ◽  
Sjoerd P. van Marle ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Human Subjects ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Healthy Human ◽  
Healthy Human Subjects

scholarly journals Clinical pharmacology of nitrendipine - Single- and multiple-dose study in Japanese healthy subjects.

1988 ◽  
Vol 19 (4) ◽  
pp. 689-706 ◽  
Author(s):  
Akio EBIHARA ◽  
Akio FUJIMURA ◽  
Hiroyuki KAJIYAMA ◽  
Kyoichi OHASHI ◽  
Kazuoki KONDO ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Healthy Subjects ◽  
Multiple Dose ◽  
Multiple Dose Study ◽  
Dose Study
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