Pharmacokinetics of a novel agent, R667, in patients with emphysema.
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.
Chiu
Yu-Yuan
YY
Hoffmann-La Roche Inc., Pharma Development Medical Pharmacology, Nutley, NJ 07110, USA. yu-yuan.chiu@roche.com
Roth
Michael D
MD
Kolis
Stanley
S
Rogovitz
David
D
Davies
Brian
B
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
D011720:Pyrazoles; C511499:R667 compound