ABSTRACT
AIMS: 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.
