ABSTRACT
This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bilirubin , Blood , Coronary Disease , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacokinetics , Metabolic Clearance Rate , Models, Biological , Phenanthrenes , Blood , PharmacokineticsABSTRACT
Objective To analyze the relationship between glyeated hemoglobin,blood pressure and carotid ar- tery atheroselerosis (AS) in non-diabetic patients.Methods To recruite 300 non-diabetic patients and retrospec tively study the relationship between glycated hemoglobin HbAlc,blood pressure and carotid artery AS.Carotid AS was determined by carotid uhrasound.Carotid AS was defined as intima-media thickness (IMT) of common ca- rotid artery≥0.9 mm,or occurrence of carotid plaque.Results Compared with the carotid AS negative subjects, the carotid AS positive patients had significant higher fasting glucose,2 h glucose,HbAlc and systolic blood pres- sure (SBP) level,without difference in DBP.Higher HbAlc or SBP levels were associated with increased incidence of carotid AS.For patients with similar SBP levels,higher HbAlc was associated with more prevalence of carotid AS.Logistic regression analysis shows HbAlc (OR=4.1,P=0.009) was an independent predictor of carotid AS,after adjusting for sex,BMI,SBP,DBP,LDL-C,HDL-C,hypersensitive C-reactive protein (hsCRP),and fasting and 2 h glucose.Conclusion These results suggests that even a slight increase of HbAlc may be independ- ently associated with carotid AS in non-diabetic subjects;and the coexistence of elevated systolic blood pressure syn- ergetically enhance the carotid atherosclerosis.