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Pharmacokinetics, Pharmacodynamics, and Safety of the 5‐HT 1B/1D Agonist Eletriptan following Intravenous and Oral Administration
Author(s) -
Milton K. Ashley,
Scott Nicholas R.,
Allen Michael J.,
Abel Samantha,
Jenkins Vivienne C.,
James GerryC.,
Rance David J.,
Eve Malcolm D.
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700222011580
Subject(s) - pharmacokinetics , medicine , pharmacology , pharmacodynamics , tolerability , volume of distribution , oral administration , cmax , crossover study , bioavailability , onset of action , adverse effect , anesthesia , placebo , alternative medicine , pathology
Four separate studies were conducted to examine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of eletriptan, a 5‐HT 1B/1D receptor agonist being developed for the treatment of migraines, after oral and intravenous administration. Fifty‐five males received oral (1.5–30 mg or 30–120 mg) or intravenous (1.67‐50 μg/kg or 50–102 μg/kg) eletriptan in four double‐ and single‐blind, placebo‐controlled, ascending‐dose crossover studies. The maximum plasma concentration (C max ) and area under the concentration curve (AUC) appeared linear over all dose ranges, with an apparent terminal half‐life of 4 to 5 hours. Clearance and volume of distribution remained constant with dose. The time to first occurrence of C max (t max ) for oral eletriptan was approximately 1 hour and was unaffected by dose. Comparison of AUC values suggested an absolute bioavailability of approximately 50%. A linear PK/PD model, fitted to the data, predicted small, transient elevations in diastolic blood pressure following eletriptan doses ± 60 mg. These effects were considered unlikely to be clinically significant. Eletriptan was well tolerated, and treatment‐related adverse events were mild to moderate and transient. These PK properties should result in eletriptan having a rapid onset and sustained duration of action in terms of migraine efficacy.