Multiple-dose pharmacokinetics of intranasally administered IS-159 in healthy subjects.
This study was designed to investigate the multiple-dose pharmacokinetics of a range of intransal doses of IS-159, a serotonin 1B/1D receptor agonist. Intranasal doses of 1, 2, 4 and 6 mg of IS-159 were administered twice at an interval of 4 hours to 17 healthy male and female subjects in a two-way crossover study. Plasma concentrations of IS-159 were determined from blood samples taken at regular intervals up to 24 hours after the first administration during both treatment periods. IS-159 was rapidly absorbed and eliminated with a t(max) of approximately 15 min and a t(1/2) of approximately 1.6 hours. With increasing dose, the exposure increased dose-proportionally, and IS-159 pharmacokinetics appear not to be influenced by gender and food intake. The results showed dose-proportional pharmacokinetics of IS-159 in the dose range tested and a low propensity for drug accumulation.
D000281:Administration, Intranasal; D000328:Adult; D018592:Cross-Over Studies; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012727:Sex Characteristics
D004151:Dipeptides; D007211:Indoles; D017366:Serotonin Receptor Agonists; C411163:2-(3-(2-aminoethyl)-1H-indol-5-yloxy)acetyl-L-tyrosyl-glycinamide