Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Psilocybin/Psilocin
| Autor: | Jogarao V. S. Gobburu, Paul R. Hutson, Elyes Dahmane |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
QTC PROLONGATION
Adult Male Pharmaceutical Science Pharmacology 030226 pharmacology & pharmacy QT interval Models Biological Psilocybin 03 medical and health sciences Electrocardiography 0302 clinical medicine Heart Rate medicine Humans Pharmacology (medical) Psilocybin/Psilocin Exposure response Dose-Response Relationship Drug business.industry Confidence interval Healthy Volunteers Long QT Syndrome 030220 oncology & carcinogenesis Psilocin Hallucinogens Female business medicine.drug |
| Zdroj: | Clinical pharmacology in drug developmentReferences. 10(1) |
| ISSN: | 2160-7648 |
| Popis: | Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to psilocin upon absorption. The potential for psilocin proarrhythmic effect was assessed using a concentration-QTc interval (C-QTc) analysis from an open-label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C-QTc relationship. At the clinical dose of 25 mg, the mean psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half-life of psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model-predicted mean ΔQTcF crossed 10 milliseconds at a psilocin concentration of 31.1 ng/mL. At a supraclinical psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C-QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text