Pharmacokinetic profile of 14C-labeled clopidogrel.

ABSTRACT

In order to obtain a global assessment of circulating clopidogrel-related products and of the excretion of the drug, the pharmacokinetic behavior and the excretion balance of 14C radioactivity following the administration of a single dose of 75 mg of 14C-labeled clopidogrel were compared in 6 clopidogrel-free healthy male subjects (Period I) and after 7 days of once daily therapy with the unlabeled drug in these subjects (at steady state) (Period II). The two study periods were separated by a 4-week washout period. For each administration of 14C-clopidogrel, blood samples were collected before and at regular intervals over 28 days after administration of the radiolabeled drug. Expired air samples were collected before and over 24 hours after the administrations of 14C-clopidogrel. All urine voided and all stools were collected before and for up to 120 hours after the administration of 14C-clopidogrel, in consecutive periods of 12 to 24 hours. The mean radiocarbon plasma concentration profiles after administration of 14C-clopidogrel given as a single dose (Period I) and during steady state (Period II) were superimposable. There were no statistically significant differences between the two treatments for any parameters. A Cmax of 3.9 mg-Eqv/L was reached after a median time of 1 hour (Tmax). The plasma elimination half-life, t1/2, ranged from 336 hours to 672 hours in Period I and from 275 to 433 hours in Period II. The radiocarbon excretion over 10 to 12 hours post-dose (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 and 46 % after administration at steady state. The cumulative fecal recovery over 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 biodisposition of the drug remains unaltered compared to a single dose.