Details

Autor(en) / Beteiligte

• Kosoglou, Teddy
• Kraft, Walter K.
• Kumar, Bharath
• Statkevich, Paul
• Xuan, Fengjuan
• Ma, Lei
• Jennings, Lisa K.
• Schiller, James E.
• Langdon, Ronald B.
• Cutler, David L.

Titel

Pharmacokinetics and pharmacodynamics of the novel PAR-1 antagonist vorapaxar in patients with end-stage renal disease

Ist Teil von

• European journal of clinical pharmacology, 2012-07, Vol.68 (7), p.1049-1056

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose To determine whether impaired renal function alters the pharmacokinetics (PK) of vorapaxar or its ability to inhibit thrombin receptor agonist peptide (TRAP)-induced platelet aggregation. Methods This was an open-label study in which 8 patients with end-stage renal disease (ESRD) on hemodialysis and 7 matched (based on age, gender, weight, and height) healthy controls were administered a single 10-mg oral dose of vorapaxar. Blood samples for vorapaxar PK and pharmacodynamic analysis were collected predose and at frequent intervals up to 6 weeks postdose. Results Mean vorapaxar bioavailability (based on area under the curve of plasma vorapaxar concentration over time) was identical in the two subject groups; the ESRD/healthy geometric mean ratio (GMR, expressed in percent) was 98. Mean maximum observed plasma concentration (77.4–98.2 ng/mL) was numerically lower in patients with ESRD compared with matched controls (GMR = 76; 90% confidence interval = 48 to 118). Median time of maximum observed plasma concentration was 2 h in both subject groups. The observed means for elimination half-life were 186 and 231 h in the ESRD and control groups, respectively. Inhibition of platelet aggregation was similar in the two groups. Four out of 15 (27%) subjects reported adverse events, all of which were characterized by the investigator as mild and unrelated to treatment. Conclusions ESRD had no clinically relevant effect on the PK profile of vorapaxar or its ability to inhibit TRAP-induced platelet aggregation.