title: Pharmacokinetics of a novel agent, R667, in patients with emphysema.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of R667, a novel emphysema agent, in patients with moderate to severe emphysema.
  
  
  METHODS
  Multiple-dose pharmacokinetics of R667 and its metabolites in emphysematous patients were studied in a multicentre, randomized, single-blind, and placebo-controlled trial. Four groups of 10 patients per group received placebo, 0.2, 0.5, or 1 mg R667 once a day for 14-16 days. On day 14 (+/-1), blood samples were taken at predose and 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h after dosing.
  
  
  RESULTS
  Pharmacokinetic analysis of the data indicated that the mean steady-state C(max) and AUC(0,tau) of R667 appeared to be dose proportional over the dose range of 0.2-1 mg when administered to emphysematous patients. Mean metabolite to R667 ratios for C(max) or AUC(0,tau) were, in general, similar across the dose range of 0.2-1 mg.
  
  
  CONCLUSIONS
  The pharmacokinetics of R667 and its metabolites appeared to be similar for patients with emphysema and healthy volunteers. Multiple-dose administration of 0.2-1 mg of R667 for up to 16 days was well tolerated in patients with emphysema.
authors.affiliation: Hoffmann-La Roche Inc., Pharma Development Medical Pharmacology, Nutley, NJ 07110, USA. yu-yuan.chiu@roche.com
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Chiu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.forename: Stanley
authors.initials: S
authors.lastname: Kolis
authors.forename: David
authors.initials: D
authors.lastname: Rogovitz
authors.forename: Brian
authors.initials: B
authors.lastname: Davies
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000097:blood* / Q000503:physiopathology; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D016037:Single-Blind Method; D014797:Vital Capacity
chemical_list: D011720:Pyrazoles; C511499:R667 compound