Drug Resistance ; Drug-Eluting Stents ; Humans ; Ticlopidine ; analogs & derivatives ; pharmacology

Genetic Variation ; Humans ; Ticlopidine ; analogs & derivatives ; pharmacokinetics ; pharmacology

This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively. The covariates including demographic characteristics, laboratory indexes, combined medication, complications and genetic polymorphisms of related enzymes were screened for their influence on the pharmacokinetic and pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data analysis was performed using NONMEM software. The general linear model and the indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic analysis were selected as the basic model, respectively. The population typical values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(-1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the covariate in the final pharmacokinetic model, and the model was to design a prior dosage regimen.
Acute Coronary Syndrome ; metabolism ; Humans ; Polymorphism, Genetic ; Ticlopidine ; analogs & derivatives ; pharmacokinetics

Drug Interactions ; Humans ; Proton Pump Inhibitors ; pharmacology ; Ticlopidine ; analogs & derivatives ; pharmacology

Toxic epidermal necrolysis (TEN) is a serious, usually drug-induced, dermatosis characterized by extensive erythema, necrosis, bullous detachment of the epidermis, constitutional symptoms, and visceral involvement. We report a 62-year-old man who was diagnosed TEN after percutaneous coronary intervention (PCI). After consulting with a cardiologist, all pre-hospital medication was discontinued except clopidogrel. With supportive care, the patient recovered.
Angioplasty, Balloon, Coronary ; Humans ; Male ; Middle Aged ; Stevens-Johnson Syndrome ; etiology ; Ticlopidine ; analogs & derivatives ; therapeutic use

This study was purposed to characterize the effect of carboxylic acid metabolite (SR26334) of clopidogrel bisulfate deprived of antiplatelet efficacy on the spectrum of gene expression in the cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and to explore the potential molecule mechanism of SR26334 impact on HUVEC. By using a Affymetrix HU133 plus 2.0 oligonucleotide microarray, the alteration of gene expression spectrum induced by SR26334 in HUVEC was detected, the real-time PCR was used to confirm the results of selected differentially expressing genes. The results indicated that total 235 including 176 up-regulated and 59 down-regulated genes were obtained with change more than 1.5-fold after SR26334 (10 µmol/L) acted on HUVEC for 48 h. SR26334 affected the expression levels of genes involved regulation of transcription, transcription, positive regulation of transcription from RNA polymerase II promoter, cell cycle, cell division, protein amino acid dephosphorylation in HUVEC. It is concluded that carboxylic acid metabolite SR26334 of clopidogrel bisulfate modulates function of endothelial cells through different pathway at gene level.
Cell Line ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; Humans ; Ticlopidine ; analogs & derivatives ; pharmacology ; Transcriptome ; drug effects

Acute Coronary Syndrome ; drug therapy ; Angioplasty, Balloon, Coronary ; Aspirin ; administration & dosage ; Humans ; Platelet Aggregation Inhibitors ; administration & dosage ; Thrombelastography ; Ticlopidine ; administration & dosage ; analogs & derivatives ; Tyrosine ; administration & dosage ; analogs & derivatives

The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.
Crystallization ; Neural Networks (Computer) ; Platelet Aggregation Inhibitors ; chemistry ; ROC Curve ; Radiographic Image Interpretation, Computer-Assisted ; Synchrotrons ; Ticlopidine ; analogs & derivatives ; chemistry ; Tomography, X-Ray Computed

PURPOSE: Hypothermia adversely affects the coagulation that could be of clinical significance in patients receiving clopidogrel. We evaluated the influence of hypothermia on transfusion requirements in patients undergoing isolated off-pump coronary artery bypass surgery (OPCAB) who continued clopidogrel use within 5 days of surgery. MATERIALS AND METHODS: Protocol-based, prospectively entered data of 369 patients were retrospectively reviewed. The time-weighted average of intraoperative temperatures and the temperature upon ICU admission (TWA-temp) was assessed. Patients were divided into normothermia (> or =36degrees C, n=224) and hypothermia (<36degrees C, n=145) group. The transfusion requirement for perioperative blood loss was assessed and compared. RESULTS: Patients with hypothermia were older and had lower body surface area (BSA) than patients with normothermia. Age and BSA adjusted transfusion requirement was significantly larger in the hypothermia group [patients requiring transfusion: 64% versus 48%, p=0.003; number of units: 0 (0-2) units versus 2 (0-3) units, p=0.002]. In multivariate analysis of predictors of perioperative multiple transfusion requirements, hypothermia was identified as an independent risk factor along with age, female gender, BSA, chronic kidney disease, and congestive heart failure. CONCLUSION: Hypothermia was associated with increased transfusion requirement in patients undergoing OPCAB who received clopidogrel in proximity to surgery. Considering the high prevalence and the possibility of hypothermia being a modifiable risk factor, aggressive measures should be undertaken to maintain normothermia in those patients.
Aged ; Coronary Artery Bypass, Off-Pump/*methods ; Female ; Humans ; Hypothermia/*physiopathology ; Male ; Middle Aged ; Retrospective Studies ; Ticlopidine/*analogs & derivatives/therapeutic use

This paper is to report the polymorphism of raw materials of clopidogrel bisulfate at home and abroad. By the analysis of Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (p-XRD), samples are roughly classified into two groups, except one patent material. And the differential scanning calorimeter (DSC) examination showed more detailed information for these materials. The results of the study could provide comprehensive basis for the quality evaluation of clopidogrel bisulfate.
Calorimetry, Differential Scanning ; Crystallization ; Evaluation Studies as Topic ; Platelet Aggregation Inhibitors ; chemistry ; Spectroscopy, Fourier Transform Infrared ; Ticlopidine ; analogs & derivatives ; chemistry ; X-Ray Diffraction