A pharmacokinetic comparison of anrukinzumab,an anti- IL-13 monoclonal antibody,among healthy volunteers,asthma and ulcerative colitis patients

AimsAnrukinzumab is an anti-IL13 monoclonal antibody. The goals of this study are to characterize the pharmacokinetics of anrukinzumab in healthy volunteers and different disease states and to identify covariates.MethodsA population pharmacokinetic (PK) model was developed in NONMEM, using data from five clinical studies including healthy volunteers, asthma and ulcerative colitis (UC) patients. Different dosing regimens including different routes of administration were also included in the data.ResultsThe PK of anrukinzumab were described by a two compartment model with first order absorption and elimination. The population estimates (relative standard error) of the volumes of distribution in the central (V_c) and peripheral (V_p) compartments were 3.8 (4.6%) and 2.2 l (8.7%), respectively. In non-UC patients, the population estimate of the systemic clearance (CL) and inter-compartmental CL was 0.00732 l h^–1 (4.9%) and 0.0224 l h^–1 (15.4%). For subcutaneous administration, the absorption rate constant was 0.012 h^–1 (6.6%) and bioavailability was nearly 100% in healthy and mild to moderate asthma patients. Both V and CL increased with body weight. CL (but not V) decreased with increasing baseline albumin concentrations. UC patients had an increased CL of 72.3% (10.5%), after correction for differences in body weight and albumin. Moderate to severe asthma patients had decreased bioavailability compared with other populations.ConclusionsAnrukinzumab''s PK behave like a typical antibody. UC patients were identified to have a faster CL of anrukinzumab than healthy volunteers and asthma patients. This finding suggests a higher dose level may be required for this population.     

Associations of common SNPs in the SORT1, GCKR,LPL, APOA1, CETP,LDLR, APOE genes with lipid trait levels in an Algerian population sample

Genome-wide association studies have identified many lipid-associated loci primarily in European and Asian populations. In view of the differences between ethnic groups in terms of the frequency and impact of these variants, our objective was to evaluate the relationships between eight lipid-associated variants (considered individually and in combination) and fasting serum triglyceride, total cholesterol, HDL- and LDL-cholesterol levels in an Algerian population sample (ISOR study, n = 751). Three SNPs (in SORT1, CETP and GCKR) were individually associated with lipid level variations. Moreover, the risk allele scores for total cholesterol, triglyceride and LDL-C levels (encompassing between three and six SNPs) were associated with their corresponding lipid traits. Our study is the first to show that some of the lipid-associated loci in European populations are associated with lipid traits in Algerians. Although our results will have to be confirmed in other North African populations, this study contributes to a better understanding of genetic susceptibility to lipid traits in Algeria.     

Sex determination from carpal bone volumes: A Multi Detector Computed Tomography (MDCT) study in a Malaysian population

PurposeThe use of Multi Detector Computed Tomography (MDCT) volume measurements of bones for sex determination allows fragile, fragmented human remains to be assessed without compromising the specimen. We set out to assess the ability of MDCT carpal bone volume measurement in determining sex in a Malaysian population.Materials and methods52 healthy volunteers were scanned in a 16-slice MDCT, and the volume of 104 sets of carpal bones was measured using a Syngo workstation (Both CT and workstation-Siemens Healthcare, Erlangen, Germany).ResultsMale carpal bones were of higher volume compared to the female carpal bones (p < 0.001). Area under the curve (AUC) assessment of responder-operator characteristics curves showed that the trapezium bone was best able to predict sex with an AUC of 0.986. At a trapezium bone volume of ⩾1.94 cm³, there was a 93.5% probability that the subject was male. Binary logistic regression analysis found that the highest accuracy was derived using the pisiform, trapezium and capitate bones. There was a strong relationship between sex prediction and grouping of the carpal bone volumes (Nagelkerke R² = 0.923) with an overall prediction accuracy of 97%.ConclusionAll 8 carpal bones exhibit sexual dimorphism to varying degrees. A binary regression analysis combining the 5 carpal bones with the highest predictive values for sex produces an accurate predictive model.     

Differences by gender in completed suicides in a Mexican population: A psychological autopsy study

ObjectiveUsing the method of psychological autopsy, we identified differences by gender in socio-demographic aspects, signs and symptoms, and suicide characteristics in a population of the state of Tabasco. Mexico.MethodsBetween the years 2007–2014, 182 psychological autopsies were documented by the Secretary of Health of the State of Tabasco, Mexico. A structured questionnaire was used to obtain information on socio-demographic aspects and suicide characteristics.ResultsThe sample was mainly formed by males (78%). 84% of the sample used hanging as suicide method. However, in comparison with the male group, females were older on the average (p = 0.002); they were mostly housewives (37.5%) and had more years of schooling (p = 0.004). Other significant differences predominantly present in the male group were: the use of alcohol at the time of suicide (52.1%), job retirement, and increases in apathy (50.7%) and aggressiveness (36.6%) (p < 0.05).ConclusionOur results suggest that there are differences by gender between subjects with completed suicide. Factors such as alcohol consumption, job retirement, aggressiveness and isolation/social apathy certainly render men more vulnerable to suicide in the Mexican population.     

Population pharmacokinetics of edoxaban in patients with symptomatic deep‐vein thrombosis and/or pulmonary embolism—the Hokusai‐VTE phase 3 study

AimsThis study characterized the population pharmacokinetics of edoxaban in patients with symptomatic deep‐vein thrombosis and/or pulmonary embolism in the Hokusai‐VTE phase 3 study. The impact of the protocol‐specified 50% dose reductions applied to patients with body weight ≤ 60 kg, creatinine clearance (CL_cr) of 30 to 50 ml min^–1 or concomitant P‐glycoprotein inhibitor on edoxaban exposure was assessed using simulations.MethodsThe sparse data from Hokusai‐VTE, 9531 concentrations collected from 3707 patients, were pooled with data from 13 phase 1 studies. In the analysis, the covariate relationships used for dose reductions were estimated and differences between healthy subjects and patients as well as additional covariate effects of age, race and gender were explored based on statistical and clinical significance.ResultsA linear two‐compartment model with first order absorption preceded by a lag time best described the data. Allometrically scaled body weight was included on disposition parameters. Apparent clearance was parameterized as non‐renal and renal. The latter increased non‐linearly with increasing CL_cr. Compared with healthy volunteers, inter‐compartmental clearance and the CL_cr covariate effect were different in patients (+64.6% and +274%). Asian patients had a 22.6% increased apparent central volume of distribution. The effect of co‐administration of P‐glycoprotein inhibitors seen in phase 1 could not be confirmed in the phase 3 data. Model‐based simulations revealed lower exposure in dose‐reduced compared with non‐dose‐reduced patients.ConclusionsThe adopted dose‐reduction strategy resulted in reduced exposure compared with non‐dose‐reduced, thereby overcompensating for covariate effects. The clinical impact of these differences on safety and efficacy remains to be evaluated.     

骨质疏松症的治疗进展及面临的挑战

骨质疏松症是世界范围内最常见的骨骼疾病,以骨量减少、结构破坏、易发生骨折为特点,易导致患者死亡或终身残疾,对患者和社会造成沉重经济负担。如何有效治疗骨质疏松症,预防骨折的发生成为医学界亟待解决的问题。本文就骨质疏松症药物治疗的新进展,以及高危特殊患病人群的治疗所面临的挑战做一综述。     

健康支持性环境对四川农村人群的不同血压水平的影响分析

目的 探讨健康支持性环境中的不同特征变量对四川省农村人群的不同血压水平的影响。方法 采用多阶段整群抽样的方法，随机抽取四川省7个县（区）8400名的18岁以上常住居民为调查对象。问卷调查一般人口学特征、身体活动行为特征和环境等信息。采用标准方法测量身高、体重、腰围和血压。采用无序多分类logistic回归分析。结果 本调查人群中共检出正常高值血压者4270例，检出率为50.83%，标化率为37.02%，平均年龄（56.22±14.89）岁；高血压患者1498例，检出率为17.83%，标化率为7.92%，平均年龄（65.26±11.28）岁。无序多分类logistic回归结果显示，住宿环境好、获得运动方面的健康信息和参与中等强度活动150Symbol~A@300min/周是正常高值血压和高血压人群的共同保护因素；住宿便利（OR=0.789, 95%CI:0.649~0.958, P=0.017）、医疗服务可及性便利（OR=0.686, 95%CI:0.509~0.924, P=0.013）、对健身步道和健身广场满意为高血压人群的保护因素。结论 多途径合理构建健康支持性环境，对农村正常高值血压者和高血压患者具有保护作用，对遏制农村高血压的流行现状起到一定作用。