A substantial portion of patients at risk for
acute coronary syndrome (ACS) are >65 years old.
Prasugrel is a novel
antiplatelet agent approved for the treatment of ACS patients undergoing
percutaneous coronary intervention, and will be used in this population. This study assessed the effect of age >/=65 years on the
pharmacokinetics (PK) and
pharmacodynamics (PD) of the
active metabolite (R-138727) of
prasugrel in healthy subjects taking
aspirin (
acetylsalicylic acid). This was an open-label, single-sequence trial conducted in a single clinical research centre in the UK. A total of 17 subjects
aged 65-80 years and 15 subjects
aged 20-39 years received a
prasugrel 5-mg once-daily
maintenance dose for 10 days followed by 10-mg once daily
maintenance doses for 10 days. All subjects also received
aspirin 75 mg daily. Serial
blood samples were collected pre-dose and at various times post-dose for measurement of the
active metabolite of
prasugrel in plasma on days 10 and 20, following the last 5- and 10-mg
prasugrel dose, respectively. PK parameters of the
active metabolite of
prasugrel included area under the plasma concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration (AUC(last)), maximum plasma concentration (C(max)) and time to C(max) (t(max)). Maximal
platelet aggregation (MPA), assessed by light transmission aggregometry using
adenosine diphosphate (ADP) 20 mumol/L, was assessed at baseline and on day 10 (5-mg
maintenance dose) and day 20 (10-mg
maintenance dose).
Bleeding times (BTs) were determined on days -5, 1, 10, 11, 20 and 21 using a modified Ivy technique. AUC(last) did not differ significantly between age groups. The steady-state trough MPA to ADP 20 mumol/L during 10-mg maintenance
dosing was 30.6% and 26.6% in
elderly and young subjects, respectively.
Mean MPA was consistently higher in
elderly subjects compared with young subjects; however, differences were generally less than ten
percentage points. BTs did not differ between the two populations during 5-mg maintenance
dosing; however, during 10-mg maintenance
dosing, BTs were up to 67% longer in young compared with
elderly subjects. A higher
frequency of minor
bleeding during 10-mg maintenance
dosing was observed in
elderly subjects compared with young subjects. These data indicate that
prasugrel PK and MPA were similar in healthy subjects regardless of age. Compared with younger subjects,
elderly subjects had shorter BTs but a greater
frequency of mild bleeding-related
adverse events.
