Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Mirogabalin When Coadministered With Lorazepam, Zolpidem, Tramadol, or Ethanol: Results From Drug-Drug Interaction Studies in Healthy Subjects
| Autor: | Jeanne Mendell, Alexander Currie, James Dow, Domenico Merante, Hamim Zahir, Hitoshi Ishizuka, Mendel Jansen, Ling He, Victor Dishy |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Zolpidem Adolescent Drug-Related Side Effects and Adverse Reactions Pharmaceutical Science Lorazepam Placebo Bridged Bicyclo Compounds Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Humans Drug Interactions Pharmacology (medical) 030212 general & internal medicine Tramadol Ethanol business.industry Middle Aged Healthy Volunteers Tolerability Anesthesia Pharmacodynamics Digit symbol substitution test Female business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Clinical Pharmacology in Drug Development. 7:597-612 |
| ISSN: | 2160-763X |
| Popis: | Four randomized, double-blind, placebo-controlled, 4-period drug-drug interaction studies were conducted in healthy subjects to evaluate the pharmacokinetic and pharmacodynamic (PD) interactions between mirogabalin and commonly used central nervous system depressants. Mirogabalin or placebo was administered alone or with single-dose lorazepam, zolpidem, tramadol, ethanol, or interacting drug placebo. Safety was assessed and serial samples for pharmacokinetic parameters were collected for up to 48 hours postdose. PD assessments included body sway (except tramadol), digit symbol substitution test, vertigo symptom scale short form, brief ataxia rating scale, and the Bond and Lader visual analog scale. Coadministration of mirogabalin with any of the 4 drugs did not cause any clinically relevant pharmacokinetic interactions. Peak mirogabalin concentration decreased by 28% (least squares mean ratio, 0.72; 90% confidence interval, [CI] 0.67, 0.76) following tramadol coadministration, and increased by 20% (least squares mean ratio, 1.20; 90%CI, 1.12, 1.28) following ethanol coadministration. Mirogabalin alone had little to no effect on PD parameters, but coadministration of mirogabalin with either lorazepam or ethanol increased the PD effects in body sway and digit symbol substitution test assays. Mirogabalin/lorazepam and mirogabalin/zolpidem increased occurrence of somnolence. Increased incidence of nausea and headache was noted with mirogabalin/tramadol and mirogabalin/ethanol, respectively. |
| Databáze: | OpenAIRE |
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