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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Pharmacokinetics, pharmacodynamics, and safety of the 5-HT(1B/1D) agonist eletriptan following intravenous and oral administration.

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 microg/kg or 50-102 microg/kg) eletriptan in four double- and single-blind, placebo-controlled, ascending-dose crossover studies. The maximum plasma concentration (Cmax) 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 Cmax (tmax) 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 > or = 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.[1]

References

  1. Pharmacokinetics, pharmacodynamics, and safety of the 5-HT(1B/1D) agonist eletriptan following intravenous and oral administration. Milton, K.A., Scott, N.R., Allen, M.J., Abel, S., Jenkins, V.C., James, G.C., Rance, D.J., Eve, M.D. Journal of clinical pharmacology. (2002) [Pubmed]
 
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