Association of CYP3A polymorphisms with the pharmacokinetics of cyclosporine A in early post-renal transplant recipients in China.

AIM: To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients. METHODS: One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clinical indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4*1G, CYP3A5*3C, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T polymorphisms. Whole blood trough concentrations of CsA at time zero (C(0)) were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted C(0) (C(0)/dose) based on several clinical indices. RESULTS: The CYP3A5*3C polymorphism influenced the C(0) and C(0)/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs (CYP3A4*1G, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T). In a univariate analysis using Pearson's correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA C(0)/dose. In the multiple regression model, CYP3A5*3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA C(0)/dose. CONCLUSION: CYP3A5*3C correlates with the C(0)/dose of CsA on the seventh day after renal transplantation. The allele is a putative indicator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.

Platelet-fibrin clot strength measured by thromboelastography could predict hypercoagulability and antiplatelet effects in patients after percutaneous coronary intervention.

BACKGROUND: It has been estimated that nearly one-fifth post-percutaneous coronary intervention (PCI) patients treated with clopidogrel continued to have recurrent thrombotic events, which implied the limitation of "one-size-fits all" strategy for antiplatelet therapy. METHODS: From July 2017 to April 2019, patients with acute coronary syndrome [ACS, including unstable angina (UA), non-ST segment elevation myocardial infraction (NSTEMI), and ST segment elevation myocardial infraction (STEMI)] or old myocardial infarction (OMI), or patients without coronary heart disease (non-CAD) were retrospectively enrolled in this study. For CAD patients undergoing PCI, standard dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) was prescribed. After administration of dual antiplatelet agents for at least 5 days, whole blood samples were collected and platelet function was tested using thrombelastography (TEG). Thrombin-induced platelet-fibrin clot strength (MAthrombin) and ADPinduced platelet-fibrin clot strength (MAADP) were measured to assess the hypercoagulability and antiplatelet effects. RESULTS: A total of 571 patients, including 479 ACS patients, 21 OMI patients and 71 non-CAD patients were enrolled. Highest level of MAthrombin was detected in STEMI patients, while lowest MAthrombin level was observed in non-CAD patients (P1 <0.05 for OMI vs. non-CAD; P2 <0.001 for ACS vs. non-CAD; P3<0.05 among ACS). Higher MAADP was also observed in STEMI and NSTEMI patients compared with UA patients (P<0.001). When MAADP was divided into trisections (MAADP <31; 31-47; >47 mm), a considerable portion of 41.8% ACS patients were in the first trisection (MAADP <31 mm), containing 50.4% of UA patients, 35.7% of NSTEMI patients and 26.5% of STEMI patients, with significant difference being observed between UA patients and other ACS patients (P<0.05 for NSTEMI vs. UA; P<0.001 for STEMI vs. UA). Meanwhile, 27.6% of NSTEMI and 31.0% of STEMI patients were in the third trisection (MAADP >47 mm), which was significantly higher than that of UA patients (12.7%) (P<0.001 for NSTEMI or STEMI vs. UA). CONCLUSIONS: Considering various degrees of hypercoagulability and antiplatelet effects of clopidogrel among OMI and ACS patients post-PCI. More attention should be paid to personalized antiplatelet therapy according to individual's effects of P2Y12 receptor inhibitors.

Efficacy and safety of tigecycline for complicated urinary tract infection: a systematic review.

BACKGROUND: Facing the global threat of emerging resistance to antibiotics, tigecycline, a novel glycylcycline antibiotic, is developed to against multidrug-resistant pathogens, but not recommended for the treatment of complicated urinary tract infection (cUTI). We performed a summary of the literatures to characterize and evaluate the efficacy and safety of tigecycline in patients with cUTI. METHODS: We searched PubMed, EMBASE, Cochrane and Clinical Trials using appropriate syntax to retrieve potential articles up to Jan 2020. General information, pathogen, medication regimen, comorbidities of patients from eligible literatures were recorded. Univariate logistic regression analysis was used to detect the potential factors associated with clinical cure. RESULTS: Nineteen articles comprising 31 cases were included. The subpopulation with transplantation (25.8% of the patients) was the most common comorbidity, and cUTIs were mainly caused by Klebsiella pneumoniae (K. pneumoniae) (48.28%) in our research. Tigecycline 100 mg per day as monotherapy was most common. Clinical cure was reported as majority (77.4%), and microbiological eradication cases accounted for the most (65.2%) among the clinical cure cases. Univariate analysis showed that K. pneumoniae caused cUTI and tigecycline as a single treatment have significant meaning to clinical outcomes (P=0.044 and P=0.034, respectively). CONCLUSIONS: Clinical and microbiological outcomes of tigecycline treatment revealed high rate of successful response. Tigecycline monotherapy may have a role in the treatment of cUTI except that caused by the pathogen K. pneumoniae. Further randomized controlled trials was still needed to evaluate tigecycline monotherapy for cUTI.