Population Pharmacokinetic/Pharmacodynamic Modeling of Clopidogrel in Korean Healthy Volunteers and Stroke Patients

Title
Population Pharmacokinetic/Pharmacodynamic Modeling of Clopidogrel in Korean Healthy Volunteers and Stroke Patients
Author(s)
이주미[이주미]황용하[황용하]강원구성숙진[성숙진]이해원[이해원]임동석[임동석]손동렬[손동렬]한성훈[한성훈]윤영란[윤영란]임미선
Keywords
CORONARY-ARTERY-DISEASE; INDIVIDUAL RESPONSIVENESS; HUMAN PLASMA; OPEN-LABEL; ASPIRIN; BIOEQUIVALENCE; VARIABILITY; METABOLITE; EVENTS; TRIAL
Issue Date
201207
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF CLINICAL PHARMACOLOGY, v.52, no.7, pp.985 - 995
Abstract
Population pharmacokinetic (PK) and pharmacodynamic (PD) modeling of clopidogrel was developed from pooled data from healthy volunteers (n = 44) and stroke patients (n = 35). The PK modeling used plasma concentrations of the clopidogrel metabolite (SR26334), and the PD modeling used platelet aggregation. The models were developed using NONMEM and evaluated via visual predictive check (VPC). Data were analyzed by 2-compartment modeling with Erlang's absorption and first-order elimination. There was no statistically significant covariate for each model parameter. The typical point estimates of PK were k(tr) (identical transfer rate constant) = 5.97 h(-1), k(e) (elimination rate constant) = 0.126 h(-1), k(d) (distribution rate constant) = 0.212 h(-1), V-2 (volume of central compartment) = 21.0 L, and V-3 (volume of peripheral compartment) = 38.8 L. The typical point estimates of PD were kin (input rate) = 27.9 h(-1), E-max (maximum effect on input rate) = 0.292 h(-1), EC50 (median effective concentration) = 0.00629 ng/mL, and BASE (predose aggregation) = 66.7%. The final model was used to estimate individual parameters using patient data and showed good predictions using VPC.
URI
http://hdl.handle.net/YU.REPOSITORY/27716http://dx.doi.org/10.1177/0091270011409228
ISSN
0091-2700
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약학대학 > 약학부 > Articles
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