Pharmacokinetic profile of C-14-labeled clopidogrel

In order to obtain a global assessment of circulating clopidogrel-related p roducts and of the excretion of the drug, the pharmacokinetic behavior and the excretion balance of C-14 radioactivity following the administration of a single dose of 75 mg of C-14-labeled clopidogrel were compared in 6 clop idogrel-free healthy male subjects (Period I) and after 7 days of once dail y therapy with the unlabeled drug in these subjects (at steady state) (Peri od II), The two study periods were separated by a 4-week washout period, Fo r each administration of C-14-clopidogrel, blood samples were collected bef ore and at regular intervals over 28 days after administration of the radio labeled drug, Expired air samples were collected before and over 24 hours a fter the administrations of C-14-clopidogrel, All urine voided and all stoo ls were collected before and for up to 120 hours after the administration o f C-14-clopidogrel, in consecutive periods of 12 to 24 hours. The mean radi ocarbon plasma concentration profiles after administration of C-14-clopidog rel given as a single dose (Period I) and during steady state (Period II) w ere superimposable. There were no statistically significant differences bet ween the two treatments for any parameters. A C-max of 3.9 mg-Eqv/L was rea ched after a median time of 1 hour (T-max). The plasma elimination half-lif e, t(1/2), ranged from 336 hours to 672 hours in Period I and from 275 to 4 33 hours in Period II. The radiocarbon excretion over 10 to 12 hours post-d ose (time to last measurable radioactivity) in expired air represented 0.31 to 0.35% of the administered dose. Mean cumulative urinary excretion over 120 hours represented 41% of the dose after a single-dose administration an d 46% after administration at steady state. The cumulative fecal recovery o ver 120 hours ranged from 35 to 57% of the dose in Period I and from 39 to 59% of the dose in Period II, Mean total excretion of radioactivity was 92% of the dose during Period I and 93% during Period II. These data indicate that, following multiple-dose administration of clopidogrel, the biodisposi tion of the drug remains unaltered compared to a single dose.