Trial registrationĬlinical Research Information Service (CRIS), KCT0001299 (Registered December 5, 2014) The model may be used to further prediction inhibition of platelet aggregation by triflusal. ConclusionsĪ PK and binary probability PD model of triflusal was successfully developed for Korean healthy volunteers. The current dosing regimen was considered to be efficacious based on the EC 50 estimate of 84.9 μg/mL obtained in this study. Thus, we concluded this relationship is more like quantal concentration-response relationship. The final structure between predicted concentration C pred, i j y and the probability of inhibition of platelet aggregation (IPA) relationship was as follows: Probability of I P A = C pred, i j 19 / 84. No time delay between concentration and response was identified. A sigmoid relationship between triflusal concentration and the probability of significant inhibition with shape factor was chosen as the final PD model. The structure and the population estimates for triflusal PK were as follows: oral clearance ( CL/F) = 0.2 Weight was selected as a covariate for clearance and volume of triflusal, respectively. The time-concentration profile of HTB over the entire dosing period was described by a one-compartment model with a first-order formation rate constant for HTB. The final PK-PD model was evaluated using a visual predictive check (VPC) and bootstrap. As the PD endpoint was qualitative, we implemented binary analysis of ‘inhibition’ and ‘non-inhibition’ rather than using the actual value of the test. Using data from 34 healthy volunteers, 476 HTB plasma concentration data points and 340 platelet aggregation data points were used to construct PK and PD models respectively using NONMEM (version 6.2). All volunteers received a single oral loading dose of 900 mg of triflusal on Day 1, followed by a dose of 600 mg/day from Day 2 to 9. This study was a randomized, open-label, multiple-dose, two-period, two-treatment, comparative crossover design. In this study we investigated the dose-exposure-response relationship of a triflusal formulation by population pharmacokinetic (PK) and pharmacodynamic (PD) modeling of its main active metabolite, hydroxy-4-(trifluoromethyl) benzoic acid (HTB).
Triflusal is a drug that inhibits platelet aggregation.
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