Population Pharmacokinetics Analysis of Mitiglinide in Chinese Healthy Volunteers / 中国药师

Objective:To establish the population pharmacokinetics model of mitiglinide given by oral route in Chinese healthy volunteers using nonlinear mixed effect model (NONMEM), investigate the pharmacokinetic characteristics of mitiglinide in Chinese healthy people to evaluate the factors that can influence the clinical pharmacokinetics of mitiglinide .Methods: Clinical data from 22 healthy volunteers were collected and the experiment was with single-dose administration.The volunteers were given 10 mg mitiglinide calcium orally and mitiglinide plasma concentration was determined by LC-MS/MS.The data was analyzed by the first order conditional estimation, and the influences of fixed effect factors such as demographic index and biochemical index were quantitatively evaluated . The population pharmacokinetics model of mitiglinide was established , and the result was verified by using the VPC and self-test meth-od.Results:The result showed that mitiglinide pharmacokinetics was fit single-compartment model .The inter-individual variability could be described by an exponential model .The typical values including central volume of distribution , clearance and absorption con-stant was 2.4 L· h-1(24％), 9.82 L(4％) and 6.46 h-1(14％), respectively.The clearance was influenced by creatinine clear-ance rate , and the absorption constant was influenced by ALT .Conclusion:The population pharmacokinetic parameters were mainly influenced by creatinine clearance rate and ALT .The established population pharmacokinetics model can explain the reasons for the in -dividual variation in the plasma concentration of mitiglinide , which can be used to guide the clinical administration of Chinese people .

Study of thyroid dysfunction in the first half of pregnancy and gestational diabetes mellitus / 实用医学杂志

Objective To explore the influence of thyroid dysfunction in the first half pregnancy (≤20 gestational weeks) on gestational diabetes. Methords By adopting the method of prospective intervention study, general data of pregnant-women in the care clinics of our hospital were collected. Thyroid function was detected and evaluated by ATA criteria. All cases were divided into two groups: normal thyroid function group and thyroid dysfunction group. The thyroid dysfunction group was intervened. 75 g OGTT were conducted in all cases in 24-28 gestational-weeks. GDM was diagnosed by IADPSG diagnostic criteria. GDM prevalence was compared between normal thyroid function group and abnormal thyroid function groups. Results 1 062 cases of pregnant women were collected. 857 cases of pregnant women were normal, while 14 cases were subclinical hyperthyroidism (1.32%), 164 cases were subclinical hypothyroidism (15.4%), 22 cases were hypothyroxinemia (2.07%). Compared with normal thyroid function, prevalence rate of GDM was the highest in hypothyroxinemia group (54.5% vs 27.8%). There was no significant difference between subclinical hypothyroidism group and normal thyroid function group. Conclusion Thyroid dysfunction in the first half pregnancy is associated with GDM , Screening and treatment of pregnant thyroid dysfunction should be attached.

Effects of glucose,insulin and uric acid on the expression of hemoglobin oxygenase in pig renal tubule cell line / 西安交通大学学报(医学版)

Objective To investigate the effects of metabolically correlated factors on pig renal tubule in cellular level by observing effects of glucose,insulin and uric acid on activity of haemachrome oxygenase in renal tubular epithelial cells.Methods Pig near renal tubular cell line(LLC-PK1) was selected as experimental object.After stimulating cells respectively with glucose(5,10,22,33mmol/L),uric acid(0,0.1,0.2,0.4mmol/L);and insulin(0,10~(-9),0~(-8),10~(-7)mol/L) in different concentrations for 48 hours,the activity of HO-1 within the cells was determined.Results In uric acid group the activity of HO-1 was significantly increased in a concentration-dependent manner,while in glucose and insulin groups,the activity of HO-1 did not change.Conclusion After LLC-PK1 was stimulated by uric acid of different concentrations,HO-1 was induced evidently,which indicates that uric acid might affect oxidative stress in renal tubule cell line.