Safety, Pharmacokinetics, and Pharmacodynamics of ASP3662, a Novel 11β‐Hydroxysteroid Dehydrogenase Type 1 Inhibitor, in Healthy Young and Elderly Subjects
| Autor: | Nancy Yuan, Gerard J. Marek, Mark Walzer, Walter Krauwinkel, Susan Bellaire, Tianli Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Drug
Adult Male 030213 general clinical medicine Adolescent media_common.quotation_subject Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Article law.invention 03 medical and health sciences Young Adult 0302 clinical medicine Randomized controlled trial Pharmacokinetics law 11β-hydroxysteroid dehydrogenase type 1 11-beta-Hydroxysteroid Dehydrogenase Type 1 polycyclic compounds Medicine Humans General Pharmacology Toxicology and Pharmaceutics Young adult Enzyme Inhibitors media_common Aged biology Dose-Response Relationship Drug business.industry General Neuroscience lcsh:Public aspects of medicine Research lcsh:RM1-950 lcsh:RA1-1270 General Medicine Articles Middle Aged Triazoles Dose–response relationship lcsh:Therapeutics. Pharmacology Tolerability Pharmacodynamics Benzamides biology.protein Female business |
| Zdroj: | Clinical and Translational Science Clinical and Translational Science, Vol 12, Iss 3, Pp 291-301 (2019) |
| ISSN: | 1752-8062 1752-8054 |
| Popis: | Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) represents a potential mechanism for improving pain conditions. ASP3662 is a potent and selective inhibitor of 11β-HSD1. Two phase I clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single and multiple ascending doses of ASP3662 in healthy young and elderly non-Japanese and young Japanese subjects. Nonlinear, more than dose-proportional PKs were observed for ASP3662 after single-dose administration, particularly at lower doses (≤ 6 mg); the PKs at steady state were dose proportional, although the time to ASP3662 steady state was dose dependent at lower doses (≤ 2 mg). Similar PKs were observed among young Japanese, young non-Japanese, and elderly non-Japanese subjects. Specific inhibition of 11β-HSD1 occurred after both single and multiple doses of ASP3662. A marked dissociation between PKs and PDs was observed after single but not multiple doses of ASP3662. ASP3662 was generally safe and well tolerated. |
| Databáze: | OpenAIRE |
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