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1.
EClinicalMedicine ; 54: 101691, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36247927

ABSTRACT

Background: Mazdutide (also known as IBI362 or LY3305677), a novel once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, achieved 12-week body weight loss up to 6.4% at doses up to 6 mg in Chinese adults with overweight or obesity. We further explored the safety and efficacy of mazdutide dosed up to 9 mg and 10 mg. Methods: In this randomised, placebo-controlled, multiple-ascending-dose phase 1b trial, we enrolled adults (aged 18-75 years, both inclusive) with overweight (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or obesity (BMI ≥28 kg/m2) from five hospitals in China. Eligible participants were randomly assigned (2:1) within each cohort by using an interactive web-response system to receive once-weekly subcutaneous mazdutide or placebo for 12 weeks in the 9 mg cohort (3 mg weeks 1-4; 6 mg weeks 5-8; 9 mg weeks 9-12) and for 16 weeks in the 10 mg cohort (2.5 mg weeks 1-4; 5 mg weeks 5-8; 7.5 mg weeks 9-12; 10 mg weeks 13-16). The participants, investigators, study site personnel involved in treating and assessing participants in each cohort and sponsor personnel were masked to treatment allocation. The primary outcomes were safety and tolerability of mazdutide, assessed from baseline to end of follow-up in all participants who received at least one dose of the study treatment. The secondary outcomes included the change from baseline to week 12 or week 16 in body weight, waist circumference and BMI. This trial is registered with ClinicalTrials.gov, NCT04440345. Findings: Between Mar. 1, 2021 and Mar. 26, 2021, a total of 24 participants were enrolled, with eight randomly assigned to mazdutide and four to placebo in each cohort. One participant receiving mazdutide and two receiving placebo in the 10 mg cohort withdrew consent and quitted the study. No serious adverse event was reported. All treatment-emergent adverse events (TEAEs) were mild or moderate in severity and most commonly-reported TEAEs were upper respiratory tract infection, diarrhoea, decreased appetite, nausea, urinary tract infection, abdominal distension and vomiting. The mean percent change from baseline to week 12 in body weight were -11.7% (SE 1.5) for participants receiving mazdutide in the 9 mg cohort and -1.8% (1.6) for participants receiving placebo (estimated treatment difference [ETD]: -9.8%; 95% confidence interval [CI]: -14.4, -5.3; P = 0.0002). The mean percent change from baseline to week 16 in body weight were -9.5% (SE 1.7) for participants receiving mazdutide in the 10 mg cohort and -3.3% (1.9) for participants receiving placebo (ETD: -6.2%; 95% CI: -11.5, -0.9; P = 0.024). In addition, compared with placebo, mazdutide achieved more profound reductions in waist circumference and BMI. Interpretation: Mazdutide dosed up to 9 mg and 10 mg was both well tolerated and showed a favourable safety profile. High-dose mazdutide showed promising 12-week body weight loss, holding great potential for the treatment of moderate-to-severe obesity. A larger and longer phase 2 trial will further evaluate the efficacy and safety of high-dose mazdutide in Chinese adults with obesity. Funding: Innovent Biologics, Inc.

2.
Nat Commun ; 13(1): 3613, 2022 06 24.
Article in English | MEDLINE | ID: mdl-35750681

ABSTRACT

The success of glucagon-like peptide-1 (GLP-1) receptor agonists to treat type 2 diabetes (T2D) and obesity has sparked considerable efforts to develop next-generation co-agonists that are more effective. We conducted a randomised, placebo-controlled phase 1b study (ClinicalTrials.gov: NCT04466904) to evaluate the safety and efficacy of IBI362 (LY3305677), a GLP-1 and glucagon receptor dual agonist, in Chinese patients with T2D. A total of 43 patients with T2D were enrolled in three cohorts in nine study centres in China and randomised in each cohort to receive once-weekly IBI362 (3.0 mg, 4.5 mg or 6.0 mg), placebo or open-label dulaglutide (1.5 mg) subcutaneously for 12 weeks. Forty-two patients received the study treatment and were included in the analysis, with eight receiving IBI362, four receiving placebo and two receiving dulaglutide in each cohort. The patients, investigators and study site personnel involved in treating and assessing patients in each cohort were masked to IBI362 and placebo allocation. Primary outcomes were safety and tolerability of IBI362. Secondary outcomes included the change in glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and post-mixed-meal tolerance test (post-MTT) glucose levels. IBI362 was well tolerated. Most commonly-reported treatment-emergent adverse events were diarrhoea (29.2% for IBI362, 33.3% for dulaglutide, 0% for placebo), decreased appetite (25.0% for IBI362, 16.7% for dulaglutide, 0% for placebo) and nausea (16.7% for IBI362, 16.7% for dulaglutide and 8.3% for placebo). HbA1c, FPG and post-MTT glucose levels were reduced from baseline to week 12 in patients receiving IBI362 in all three cohorts. IBI362 showed a favourable safety profile and clinically meaningful reductions in blood glucose in Chinese patients with T2D.


Subject(s)
Diabetes Mellitus, Type 2 , Blood Glucose , Glucagon , Glucagon-Like Peptide 1/therapeutic use , Glucagon-Like Peptide-1 Receptor/agonists , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/adverse effects , Peptides , Receptors, Glucagon , Recombinant Fusion Proteins/adverse effects
3.
EClinicalMedicine ; 39: 101088, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34430840

ABSTRACT

BACKGROUND: IBI362 (LY3305677) is a novel weekly-dose glucagon-like peptide-1 and glucagon receptor dual agonist being developed for the treatment of obesity and type 2 diabetes. The aim of this randomised, placebo-controlled, multiple ascending dose phase 1b study was to evaluate the safety, tolerability, pharmacokinetics and efficacy of IBI362 in Chinese adults with overweight or obesity. METHODS: This study enrolled adults with overweight (body mass index [BMI]≥24 kg/m2) accompanied by hyperphagia and/or at least one comorbidity or obesity (BMI≥28 kg/m2) from six study centres in China. Eligible participants were randomised 2:1 to receive once-weekly subcutaneous injection of IBI362 or placebo in each of the three ascending dose cohorts for 12 weeks with additional 8 weeks of safety follow-up. The dose-escalation regimens were: 3.0 mg cohort (1.0 mg weeks 1-4; 2.0 mg weeks 5-8; 3.0 mg weeks 9-12); 4.5 mg cohort (1.5 mg weeks 1-4; 3.0 mg weeks 5-8; 4.5 mg weeks 9-12); 6.0 mg cohort (2.0 mg weeks 1-4; 4.0 mg weeks 5-8; 6.0 mg weeks 9-12). The participants, investigators and study site personnel involved in treating and assessing participants within each cohort were masked to treatment allocation. The primary endpoints were safety and tolerability of IBI362. This study is registered with ClinicalTrials.gov, number NCT04440345. FINDINGS: Between June 15th, 2020 and January 15th, 2021, 12 participants were enrolled and randomised in each cohort. Throughout the study, no participant discontinued the treatment due to safety reason and no serious adverse event was reported. Gastrointestinal adverse events and decreased appetite were the most common adverse events and mostly mild in severity. Three participants receiving IBI362 reported mild and asymptomatic cardiac disorders revealed by electrocardiogram. Estimated percent changes in mean body weight from baseline to week 12 were -4.81% (95%CI -6.61 to -3.02), -6.40% (-8.23 to -4.58) and -6.05% (-7.91 to -4.18) for participants receiving IBI362 in the 3.0 mg, 4.5 mg and 6.0 mg cohort, respectively, compared with 0.60% (-0.86 to 2.07) for those receiving placebo. INTERPRETATION: IBI362 was well tolerated and showed a body weight-lowering effect in Chinese adults with overweight or obesity. FUNDING: Innovent Biologics.

4.
Br J Clin Pharmacol ; 87(4): 1890-1902, 2021 04.
Article in English | MEDLINE | ID: mdl-33010043

ABSTRACT

AIMS: Voriconazole is a broad-spectrum antifungal agent for the treatment of invasive fungal infections. There is limited information about the pharmacokinetics and appropriate dosage of voriconazole in patients with liver dysfunction. This study aimed to explore the relationship between voriconazole trough concentration (Ctrough ) and toxicity, identify the factors significantly associated with voriconazole pharmacokinetic parameters and propose an optimised voriconazole dosing regimen for patients with liver dysfunction. METHODS: The study prospectively enrolled 51 patients with 272 voriconazole concentrations. Receiver operating characteristic curves were used to explore the relationship between voriconazole Ctrough and toxicity. The pharmacokinetic data was analysed with nonlinear mixed-effects method. Dosing simulations stratified by total bilirubin (TBIL, TBIL-1: TBIL < 51 µmol/L; TBIL-2: 51 µmol/L ≤ TBIL < 171 µmol/L; TBIL-3: TBIL ≥ 171 µmol/L) were performed. RESULTS: Receiver operating characteristic curve analysis revealed that voriconazole Ctrough of ≤ 5.1 mg/L were associated with significantly lower the incidence of adverse events. A 1-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Population pharmacokinetic parameters of clearance, volume of distribution and oral bioavailability were 0.88 L/h, 148.8 L and 88.4%, respectively. Voriconazole clearance was significantly associated with TBIL and platelet count. The volume of distribution increased with body weight. Patients with TBIL-1 could be treated with a loading dose of 400 mg every 12 hours (q12h) for first day, followed by a maintenance dose of 100 mg q12h administered orally or intravenously. TBIL-2 and TBIL-3 patients could be treated with a loading dose of 200 mg q12h and maintenance doses of 50 mg q12h or 100 mg once daily and 50 mg once daily orally or intravenously, respectively. CONCLUSIONS: Lower doses and longer dosing intervals should be considered for patients with liver dysfunction. TBIL-based dosing regimens provide a practical strategy for achieving voriconazole therapeutic range and therefore maximizing treatment outcomes.


Subject(s)
Invasive Fungal Infections , Liver Diseases , Antifungal Agents/adverse effects , Humans , Invasive Fungal Infections/drug therapy , Liver Diseases/drug therapy , Prospective Studies , Voriconazole/adverse effects
5.
BMC Neurol ; 19(1): 274, 2019 Nov 07.
Article in English | MEDLINE | ID: mdl-31699038

ABSTRACT

BACKGROUND: Early prediction of unfavorable outcome after ischemic stroke is of great significance to the clinical and therapeutic management. A nomogram is a better visual tool than earlier models and prognostic scores to predict clinical outcomes, which incorporates different factors to develop a graphic continuous scoring system and calculates accurately the risk probability of poor outcome entirely based on individual characteristics. However, to date, no nomogram models have been found to predict the probability of 6-month poor outcome after ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of the probability of 6-month unfavorable outcome in Chinese patients with ischemic stroke. METHODS: Based on the retrospective stroke registry, a single-center study which included 499 patients from May, 2013 to May, 2018 was conducted in Nanjing First Hospital (China) for ischemic stroke within 12 h of symptoms onset. The main outcome measure was 6-month unfavorable outcome (mRS > 2). To generate the nomogram, NIHSS score on admission, Age, previous Diabetes mellitus and crEatinine (NADE) were integrated into the model. We assessed the discriminative performance by using the area under the curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. RESULTS: A visual NADE nomogram was constructed that NIHSS score on admission (OR: 1.190, 95%CI: 1.125-1.258), age (OR: 1.068, 95%CI: 1.045-1.090), previous diabetes mellitus (OR: 1.995, 95%CI: 1.236-3.221) and creatinine (OR: 1.010, 95%CI: 1.002-1.018) were found to be significant predictors of 6-month unfavorable outcome after acute ischemic stroke in Chinese patients. The AUC-ROC of nomogram was 0.791. Calibration was good (p = 0.4982 for the Hosmer-Lemeshow test). CONCLUSION: The NADE is the first nomogram developed and validated in Chinese ischemic stroke patients to provide an individual, visual and precise prediction of the risk probability of 6-month unfavorable outcome.


Subject(s)
Nomograms , Recovery of Function , Stroke , Aged , Aged, 80 and over , Area Under Curve , Asian People , Female , Humans , Male , Middle Aged , Probability , Prognosis , ROC Curve , Registries , Retrospective Studies
6.
Front Neurol ; 10: 1100, 2019.
Article in English | MEDLINE | ID: mdl-31736848

ABSTRACT

Background and Purpose: The clinical use of tirofiban for patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of tirofiban combined with MT in AIS patients. Methods: Patients with AIS who underwent MT from January 2014 to December 2018 were enrolled in three stroke units in China. Subgroup analyses were performed based on stroke etiology which was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Safety outcomes were in-hospital intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) and mortality at 3-month. Efficacy outcomes were favorable functional outcome and functional independence at 3-month and neurological improvement at 24 h, 3 d and discharge. Results: In patients with large artery atherosclerosis (LAA) stroke, multivariate analyses revealed that tirofiban significantly decreased the odds of in-hospital ICH (adjusted OR = 0.382, 95% CI 0.180-0.809) and tended to increase the odds of favorable functional outcome at 3-month (adjusted OR = 3.050, 95% CI 0.969-9.598). By contrast, in patients with cardioembolism (CE) stroke, tirofiban was not associated with higher odds of favorable functional outcome at 3-month (adjusted OR = 0.719, 95% CI 0.107-4.807), but significantly decreased the odds of neurological improvement at 24 h and 3d (adjusted OR = 0.185, 95% CI 0.047-0.726; adjusted OR = 0.268, 95% CI 0.087-0.825). Conclusions: Tirofiban combined with MT appears to be safe and effective in LAA patients, but has no beneficial effect on CE patients.

7.
J Stroke Cerebrovasc Dis ; 28(6): 1618-1622, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30898445

ABSTRACT

BACKGROUND: Recently, the NIHSS STroke Scale score, Age, pre-stroke mRS score, onset-to-treatment Time (START nomogram) predicts 3-month functional outcome after intravenous thrombolysis in ischemic stroke patients. However, this model has not yet been an external validation. We aim to validate the performance of START nomogram. METHODS: Data were derived from the stroke center of the Nanjing First Hospital (China). Patients who lacked the necessary data to calculate the nomogram and missed 3-month modified Ranking scale scores were excluded. Modified Rankin Scale score more than 2 at 3-month was assessed as an unfavorable outcome. We used areas under the receiver operator characteristic curves (AUC-ROC) to quantify the prognostic value. Calibration was assessed by calibration plots and Hosmer-Lemeshow (HL) goodness of fit test. RESULT: The final cohort included 306 eligible patients. For 3-month unfavorable outcome, the AUC-ROC of the START nomogram was .766 (95%CI: .7013-.8304, P < .0001), suggesting good discrimination in the START nomogram. It also showed good calibration (HL goodness of fit test P = .1261) in the external validation sample. CONCLUSION: The START nomogram with good predictive performance is a reliable and simple clinical instrument to predict unfavorable outcome after acute stroke.


Subject(s)
Decision Support Techniques , Nomograms , Stroke/drug therapy , Thrombolytic Therapy/methods , Aged , Aged, 80 and over , Asian People , China/epidemiology , Databases, Factual , Disability Evaluation , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Recovery of Function , Registries , Reproducibility of Results , Risk Factors , Stroke/diagnosis , Stroke/ethnology , Stroke/physiopathology , Thrombolytic Therapy/adverse effects , Time Factors , Treatment Outcome
8.
Cerebrovasc Dis ; 47(1-2): 80-87, 2019.
Article in English | MEDLINE | ID: mdl-30897564

ABSTRACT

BACKGROUND: Accurate prognostication of unfavorable outcome made at the early onset of stroke is important to both the clinician and the patient management. This study was aimed to develop a nomogram based on the integration of parameters to predict the probability of 3-month unfavorable functional outcome in Chinese acute ischemic stroke patients. METHODS: We retrospectively collected patients who underwent acute ischemic stroke at Stroke Center of the Nanjing First Hospital (China) between May 2013 and May 2018. After exclusion, the study population includes 1,025 patients for nomogram development. The main outcome measure was 3-month unfavorable outcome (modified Rankin Scale > 2). Multivariable logistic regression analysis was used to develop the predicting model, and stepwise logistic regression with the Akaike information criterion was utilized to find best-fit nomogram model. We incorporated the creatinine, fast blood glucose, age, previous cerebral hemorrhage, previous valvular heart disease, and NHISS score (COACHS), and these factors were presented with a nomogram. We assessed the discriminative performance by using the area under curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. RESULTS: Multivariate analysis of the 1,025 patients for logistic regression helped identify the independent factors as National Institutes of Health Stroke Scale score on admission, age, previous valvular heart disease, fasting blood glucose, creatinine, and previous cerebral hemorrhage, which were included in the COACHS nomogram. The AUC-ROC of nomogram was 0.799. Calibration was good (p = 0.1376 for the Hosmer-Lemeshow test). CONCLUSIONS: The COACHS nomogram may be used to predict unfavorable outcome at 3 months after acute ischemic stroke in Chinese population. It may be also a reliable tool that is effective in its clinical utilization to risk-stratify acute stroke patients.


Subject(s)
Brain Ischemia/diagnosis , Decision Support Techniques , Nomograms , Stroke/diagnosis , Aged , Aged, 80 and over , Asian People , Brain Ischemia/epidemiology , Brain Ischemia/physiopathology , Brain Ischemia/therapy , China/epidemiology , Disability Evaluation , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Recovery of Function , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/epidemiology , Stroke/physiopathology , Stroke/therapy , Time Factors
9.
Basic Clin Pharmacol Toxicol ; 125(1): 34-43, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30715804

ABSTRACT

Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Voriconazole clearance (CL) was 0.58 L/h, the volume of distribution (Vd ) was 134 L, and oral bioavailability (F) was 80.8%. This study showed that platelet count was significantly associated with voriconazole pharmacokinetic parameters. CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Voriconazole CL was significantly decreased in patients with liver dysfunction. This study provides useful pharmacokinetics information for patients with liver dysfunction while highlighting the value of therapeutic drug monitoring in adjusting doses.


Subject(s)
Antifungal Agents/pharmacokinetics , Invasive Fungal Infections/drug therapy , Liver Diseases/physiopathology , Liver/physiopathology , Voriconazole/pharmacokinetics , Administration, Oral , Adult , Aged , Aged, 80 and over , Antifungal Agents/administration & dosage , Biological Availability , Dose-Response Relationship, Drug , Drug Monitoring , Female , Humans , Invasive Fungal Infections/blood , Invasive Fungal Infections/complications , Liver Diseases/blood , Liver Diseases/complications , Male , Metabolic Clearance Rate , Middle Aged , Models, Biological , Retrospective Studies , Voriconazole/administration & dosage
10.
Expert Rev Neurother ; 19(4): 349-358, 2019 04.
Article in English | MEDLINE | ID: mdl-30807235

ABSTRACT

BACKGROUND: About 40% of acute ischemic stroke patients are under antiplatelet pretreatment. Previous studies have shown conflicting results on the effect of prior antiplatelet agents on post thrombolytic clinical outcomes. METHODS: A systematic search using PubMed and EMBASE databases for eligible studies. Prior antiplatelet safety was measured by symptomatic intracerebral hemorrhage (sICH) and mortality. Efficacy was measured by functional independence and favorable functional outcome. RESULTS: Crude analysis indicated that antiplatelet pretreatment was associated with sICH and mortality. In adjusted analysis, the results confirmed a nonsignificant association between antiplatelet pretreatment and a higher risk of sICH and mortality, but demonstrated that antiplatelet pretreatment tended to improve functional independence and favorable functional outcome. Subgroup analysis detected a racial disparity in prior antiplatelet effect on sICH and the association between antiplatelet pretreatment and sICH was dependent on different antiplatelet regiments. CONCLUSION: There was no significant difference in sICH and mortality between patients with and without antiplatelet pretreatment. Besides, antiplatelet pretreatment did not adversely affect the efficacy outcomes. The prevalence of sICH among Asians receiving antiplatelet pretreatment was relatively high. Additionally, it needs to be noticed that the effect of preexisting antiplatelet on clinical outcomes may be dependent on post thrombolytic antiplatelet regiments.


Subject(s)
Brain Ischemia/drug therapy , Cerebral Hemorrhage/chemically induced , Fibrinolytic Agents/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Stroke/drug therapy , Brain Ischemia/mortality , Cerebral Hemorrhage/mortality , Humans , Platelet Aggregation Inhibitors/adverse effects , Stroke/mortality
11.
Clin Ther ; 40(7): 1170-1178, 2018 07.
Article in English | MEDLINE | ID: mdl-30017169

ABSTRACT

PURPOSE: Some studies in the white population have shown that carriers of at least 1 loss-of-function allele in the gene that encodes the cytochrome P-450 2C19 isozyme (CYP2C19) have lower levels of the clopidogrel active metabolite (CAM) and a reduced antiplatelet effect of clopidogrel. However, data are limited regarding the association between CYP2C19 genetic variants and exposure to CAM and on the pharmacodynamic properties of CAM in the Chinese population. Data from the white population cannot be extrapolated to the Chinese population because of the marked interethnic differences in CYP2C19 variants. This study was aimed to investigate the influence of CYP2C19 genetic polymorphisms on the pharmacokinetic properties of CAM and the antiplatelet effect of clopidogrel in healthy Chinese volunteers, and to provide evidence for the role of a CYP2C19 genotyping test in predicting the antiplatelet effect of clopidogrel in the Chinese population. METHODS: Twenty healthy subjects received a single 300-mg dose of clopidogrel and were assigned to 1 of 3 groups according to CYP2C19 genotype: CYP2C19 *1/*1 (normal metabolizers [NM]; n = 8), CYP2C19 *1/*2 or *3 (intermediate metabolizers [IM]; n = 10) and CYP2C19 *2/*2 or *3 and *3/*3 (poor metabolizers [PM]; n = 2). Blood samples were collected at baseline and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after administration. The plasma concentrations of clopidogrel and CAM were analyzed by LC-MS/MS, and adenosine diphosphate-induced platelet aggregation was measured by light-transmittance aggregometry. FINDINGS: There were no significant differences in Cmax and AUC0-t of clopidogrel prodrug in the NM group compared with the IM and PM groups. The mean CAM Cmax value was significantly higher in the NM group than in IM and PM groups (45.39 [12.57] vs 29.15 [7.92] ng/mL [P = 0.003] and 19.55 [2.19] ng/mL [P = 0.004], respectively). The mean CAM AUC0-t value was significantly higher in the NM group than in the IM and PM groups (61.05 [21.63] vs 37.67 [11.01] ng · h/mL [P = 0.007] and 27.08 [2.72] ng · h/mL [P = 0.016]). The NM group exhibited a significantly higher percentage of inhibition of platelet aggregation than did the IM or PM group (P = 0.001). The correlations between the pharmacokinetic properties (Cmax, AUC0-t) of CAM and the pharmacodynamic data (maximal and inhibition of platelet aggregation) were significant (both, Pearson r > 0.5 and P < 0.01). IMPLICATION: In these healthy Chinese subjects, carriers of CYP2C19 loss-of-function allele(s) had significantly reduced exposure of CAM and decreased levels of inhibition of platelet aggregation with clopidogrel; these genotypes therefore might be a determinant for the formation of CAM and its antiplatelet effects. Study identifier: ChiCTR-OCH-14004382.


Subject(s)
Asian People/genetics , Clopidogrel/pharmacology , Cytochrome P-450 CYP2C19/genetics , Platelet Aggregation Inhibitors/pharmacology , Adult , Clopidogrel/blood , Cytochrome P-450 CYP2C19/metabolism , Genotype , Healthy Volunteers , Humans , Male , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/blood , Polymorphism, Genetic , Young Adult
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