Intravenous Hydroxypropyl β-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial
| Autor: | Egj Hulskotte, H-P Stobernack, Dirk Kropeit, Katharina Erb-Zohar, Holger Zimmermann, Helga Rübsamen-Schaeff, J Scheuenpflug, A van Schanke |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Time Factors Visual Analog Scale 030106 microbiology Cmax Pharmacology Acetates Placebo General Biochemistry Genetics and Molecular Biology Article law.invention 03 medical and health sciences Letermovir Young Adult 0302 clinical medicine Randomized controlled trial Pharmacokinetics law medicine Humans Dosing General Pharmacology Toxicology and Pharmaceutics Adverse effect Demography Dose-Response Relationship Drug business.industry General Neuroscience Research General Medicine Articles Middle Aged 2-Hydroxypropyl-beta-cyclodextrin Dose–response relationship 030220 oncology & carcinogenesis Area Under Curve Quinazolines Administration Intravenous Female business medicine.drug |
| Zdroj: | Clinical and Translational Science |
| ISSN: | 1752-8062 |
| Popis: | Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two‐part, single‐center, randomized, double‐blind, placebo‐controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl β‐cyclodextrin (HPβCD)‐based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once‐daily doses (240 mg; 8 letermovir, 4 placebo) of HPβCD‐formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single‐dose and multiple‐dose regimens were generally well tolerated. Single‐dose escalation resulted in a slightly more‐than‐dose‐proportional increase in the area under the letermovir plasma concentration–time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (Cmax) was dose proportional. After once‐daily dosing, accumulation ratios in AUC and Cmax were 1.22 and 1.03, respectively. The terminal half‐life was 28.3 h, supporting once‐daily dosing (EudraCT Number: 2012‐001603‐20). |
| Databáze: | OpenAIRE |
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