Evaluation of the Effect of Aspirin on Platelet Aggregation: Methodological Recommendations for Aspirin-Drug Interaction Studies

Given the broad application of aspirin as antiplatelet drug, availability of standardized methodology to assess potential interaction with any co-medication on platelet aggregation is desired. We characterized the effect of aspirin (ASA) therapy on collagen-induced platelet aggregation in whole blood to define such methodology. Collagen-induced platelet whole blood aggregation was assessed in 6 healthy male volunteers on 2 occasions (Day 1, Day 7) using the Chronolog aggregometer. From Day 2 up to Day 7, subjects received a daily oral dose of 75 mg ASA. The relationship between collagen dose and platelet aggregation response was assessed. On Day 1, maximal aggregation was observed at 1 μg/mL collagen (15.3 ± 4.6 Ω) and higher. Reproducible results were obtained without any indication of intra-subject fluctuations. ASA treatment decreased maximal aggregation by 80% and 38% at 0.5 and 2.0 μg/mL collagen, respectively. Power calculations were performed based on the observed intra-subject variability and demonstrated minimal sample sizes of 9 - 11 subjects for future cross-over ASA-drug interaction studies exploring effects on platelet aggregation, which demonstrates that the proposed collagen-induced ex vivo whole blood platelet aggregation is a feasible methodology to evaluate ASA-drug interactions in healthy volunteers.

Access to novel anti-diabetic agents in resource limited settings:A brief commentary

The prevalence of diabetes mellitus is increasing in resource limited settings.Simultaneously,there has been an increase in the number of novel therapies for the management of diabetes mellitus.However,use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings.Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes,and thus most likely to benefit from the therapy,are less likely to have negative budget impact for funders.To improve access,and reduce morbidity and mortality,requires alignment amongst key stakeholders including patient advocacy groups,health care professional councils,national departments of health,the pharmaceutical industry,treasury and finance departments.

Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in nonsmall cell lung cancer

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma(NSCLC),we performed a two-cohort of genome-wide association studies(GWAS),including 34 for WES-based and 433 for microarray-based analyses,as well as two independent validation cohorts.After integrating the results of two studies,the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples,and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments.We found that a total of 68 variations were significant at P<1×10^(-3)in cohort 1 discovery stage,of which 3 SNPs were verified in 262 independent samples.A total of541 SNPs were significant at P<1×10^(-4)in cohort 2 discovery stage,of which 8 SNPs were verified in 347 independent samples.Comparing the validated SNPs in two GWAS,ADCY1 gene was verified in both independent studies.The results of fine-mapping showed that the G allele carriers of ADCY1rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy.In conclusion,our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.