Effects of Lasmiditan on Cardiovascular Parameters and Pharmacokinetics in Healthy Subjects Receiving Oral Doses of Propranolol

Autor: Darren Wilbraham, Paul A. Ardayfio, Michael Case, Max Tsai, Helen Hochstetler
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Pyridines
Pharmaceutical Science
Administration
Oral
Blood Pressure
Pharmacology
030226 pharmacology & pharmacy
Cardiovascular System
chemistry.chemical_compound
0302 clinical medicine
drug‐drug interaction
Piperidines
Heart Rate
vasoconstriction
Pharmacology (medical)
migraine
Drug Interactions
Articles
Fasting
Middle Aged
Lasmiditan
Healthy Volunteers
Serotonin Receptor Agonists
030220 oncology & carcinogenesis
Benzamides
lasmiditan
Drug Therapy
Combination
Female
medicine.symptom
pharmacokinetics
medicine.drug
Agonist
Adult
medicine.drug_class
Migraine Disorders
Adrenergic beta-Antagonists
Original Manuscript
Propranolol
03 medical and health sciences
Pharmacokinetics
Heart rate
medicine
Humans
propranolol
Aged
business.industry
medicine.disease
Blood pressure
Migraine
chemistry
business
Vasoconstriction
cardiovascular effects
Zdroj: Clinical Pharmacology in Drug Development
ISSN: 2160-7648
2160-763X
Popis: Lasmiditan (LY573144/COL‐144) is a high‐affinity, centrally penetrant, selective 5‐HT1F receptor agonist currently under investigation for acute treatment of migraine. Although lasmiditan is not known to induce vasoconstriction, it remains important to understand its effect on cardiovascular parameters because it is likely to be coadministered with β‐adrenergic receptor antagonists used for migraine prophylaxis, such as propranolol. This phase 1, single‐center, open‐label, fixed‐sequence study evaluated the cardiovascular and pharmacokinetic effects of 200 mg lasmiditan in 44 healthy subjects receiving repeated oral doses of twice‐daily 80 mg propranolol under fasting conditions. Coadministration caused statistically significant decreases in mean hourly heart rate relative to propranolol alone, but the maximum magnitude of this effect was –6.5 bpm and recovered to predose levels by 3 to 4 hours before stabilizing. Additionally, short‐lived (≤2.5 hours) statistically significant increases in systolic blood pressure (8.3 mm Hg) and diastolic blood pressure (6.4 mm Hg) were observed following coadministration. Consistent with the largely nonoverlapping metabolic pathways of lasmiditan and propranolol, exposure to either drug was not affected by coadministration. Overall, compared with administration of either drug alone, coadministration was generally well tolerated.
Databáze: OpenAIRE
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