title: Pharmacokinetics and tolerability of oral rizatriptan in healthy male and female volunteers.
abstract: OBJECTIVE
  The pharmacokinetics and dose proportionality of rizatriptan single oral doses from 2.5 to 15 mg administered as solutions to healthy volunteers were studied.
  
  
  METHODS
  In a randomized, crossover study with four periods, twenty-four healthy volunteers (12 males and 12 females) took single oral doses of 2.5, 5, 10, and 15 mg rizatriptan in Periods 1-4. In a fifth period, subjects received 4 mg intravenous (i.v.) rizatriptan as a reference. Plasma and urine rizatriptan concentrations were determined at several timepoints/intervals for 12 and 24 h, respectively.
  
  
  RESULTS
  The arithmetic mean AUC values following single oral doses of 2.5, 5, 10, and 15-mg rizatriptan were 16, 33, 72, and 127 ng ml-1 h, respectively, in males; and 19, 42, 97, and 161 ng ml-1 h, respectively, in females. The overall bioavailability (F ) of rizatriptan was approximately 40% in males. Following the 4 mg reference i.v. dose, the apparent plasma clearance (CL) and renal clearance (CLr ) were 1042 and 225 ml min-1, respectively, in males; and 821 and 174 ml min-1, respectively, in females.
  
  
  CONCLUSIONS
  The disposition kinetics of oral rizatriptan were linear for doses of 2. 5-10 mg in males, and for doses of 2.5-5 mg in females. However, the degree of nonlinearity for higher doses was minor for both genders. The plasma concentrations of rizatriptan were slightly greater in women compared to men but the difference was not considered to be clinically meaningful. Also, the clearance of rizatriptan appeared to be mainly nonrenal.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.forename: J A
authors.initials: JA
authors.lastname: Conroy
authors.forename: M E
authors.initials: ME
authors.lastname: Stepanavage
authors.forename: C M
authors.initials: CM
authors.lastname: Mendel
authors.forename: G
authors.initials: G
authors.lastname: Somers
authors.forename: D A
authors.initials: DA
authors.lastname: McLoughlin
authors.forename: T V
authors.initials: TV
authors.lastname: Olah
authors.forename: M
authors.initials: M
authors.lastname: De Smet
authors.forename: B
authors.initials: B
authors.lastname: Keymeulen
authors.forename: J D
authors.initials: JD
authors.lastname: Rogers
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018592:Cross-Over Studies; D005260:Female; D008297:Male; D051379:Mice; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D012737:Sex Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014363:Tryptamines
chemical_list: D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan