title: Population pharmacokinetic analyses to evaluate the influence of intrinsic and extrinsic factors on exposure of prasugrel active metabolite in TRITON-TIMI 38.
abstract: Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON-TIMI 38 was undertaken. A multilinear regression model was used to quantitatively predict prasugrel's active metabolite (Pras-AM) concentrations from its 2 downstream inactive metabolites. Population-based methods were then applied to Pras-AM concentration data to characterize the PK. The potential influence of body weight, body mass index, age, sex, renal function, diabetes, tobacco use, and other disease status on Bayesian estimates of Pras-AM exposures was assessed. The PK of Pras-AM was adequately described by a multicompartmental model and consistent with results from previous studies. The systemic exposure of prasugrel was not appreciably affected by body mass index, gender, diabetes, smoking, and renal impairment. Pras-AM mean exposure in patients weighing <60 kg (4.1%) was 30% (90% confidence interval [CI] 1.16-1.45) higher than exposure in patients > or =60 kg. Mean Pras-AM exposures for patients > or =75 years (10.5%) were 19% (90% CI: 1.11-1.28) higher compared with patients <75 years.
authors: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. wrishkore@lilly.com
authors: Rebecca E
authors: RE
authors: Wrishko
authors: C Steven
authors: CS
authors: Ernest
authors: David S
authors: DS
authors: Small
authors: Ying G
authors: YG
authors: Li
authors: Govinda J
authors: GJ
authors: Weerakkody
authors: Jeffrey R
authors: JR
authors: Riesmeyer
authors: William L
authors: WL
authors: Macias
authors: Shashank
authors: S
authors: Rohatagi
authors: Daniel E
authors: DE
authors: Salazar
authors: Elliott M
authors: EM
authors: Antman
authors: Stephen D
authors: SD
authors: Wiviott
authors: Eugene
authors: E
authors: Braunwald
authors: Lan
authors: L
authors: Ni
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001835:Body Weight; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010879:Piperazines / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D000068799:Prasugrel Hydrochloride; D011355:Prodrugs; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000493:pharmacokinetics*
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; C510685:R-138727; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride