The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.
Algorithms ; Bayes Theorem ; Carbamazepine ; analogs & derivatives ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Regression Analysis ; Tacrolimus ; pharmacokinetics

OBJECTIVE:To focus on the phenomenon of medication socialization.METHODS:Referenced by the related literature,different social factors affecting medication socialization were analyzed from the perspective of social pharmacy.RESULTS&CONCLUSION:The social factors affecting medication socialization were patients,pharmaceutical enterprises,governmental regulatory agencies,pharmacologists,new technologies,hospitals,doctors etc.To prevent medication from over-socialization effectively,medical professionals’roles should be brought into full play,people’s consciousness of rational drug use should be strengthened,enterprises’attention to the social effects should be emphasized,and governmental supervi-sion should be strengthened,meanwhile correct public opinion orientations should be followed.

Knee osteoarthritis (KOA) is a common degenerative joint disease. Biomechanics of lower extremity plays an important role in KOA. Foot progression angle, with the advantages of non-invasive, convenience, has been attached great importance by people gradually. Changing foot progression angle may effect the knee adduction torque, tibia rotation, muscle activity, which leads to change the load of the knee joint, and alleviate the pain, improve the function of knee joint and the quality of life of the patients.

Hemiplegics after stroke are often disabled in sit-to-stand(STS).This article discussed the biomechanics of STS in the hemiplegic stroke patients,in terms of kinematics,kinetics and surface electromyography,and the rehabilitation for the stroke patients with STS dysfunction.It was found that the stability,duration,symmetry of support and degree and se-quence of muscular activation were different when the patients finished the STS task in three foot positions of natural, symmetrical and unaffected foot behind.The early STS rehabilitation training or other rehabilitation may improve the function of the hemiplegic lower extremity to prevent falls and apraxia.

This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation method to estimate individual pharmacokinetic parameters based on D-optimal sampling strategy. Meanwhile, the performance of MAPB was compared with the multiple linear regression (MLR) method in terms of accuracy and precision. Pharmacokinetic study of pioglitazone was employed as the example case. The population pharmacokinetics was characterized by nonlinear mixed effects model (NONMEM). The sparse sampling strategy (1-4 points) was identified by D-optimal algorithm using WinPOPT software. The simulated data generated by Monte Carlo method were used to access the performance of MAPB and MLR. As the number of samples per subject decreased, the accuracy and precision of MAPB method tended to get worse. The estimation for CL and Vby MAPB using D-optimal two-point design had less bias with low inter-individual variability, and had more bias and imprecision with high residue variability. The estimation of AUC by MAPB using D-optimal 2 points design had similar accuracy and precision to MLR. However, MAPB estimation was better than MLR while adjusting the sampling time to one hour. Overall, the MAPB method had similar predictive performance as MLR, but MAPB could provide more pharmacokinetic information with higher sampling flexibility.
Area Under Curve ; Bayes Theorem ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Linear Models ; Monte Carlo Method ; Nonlinear Dynamics ; Thiazolidinediones ; pharmacokinetics

Objective To assess the value of three-dimensional contrast-enhanced ultrasonography (3D-CEUS) in evaluation of hepatic arteries variants.Methods Both two-dimensional contrast-enhanced ultrasonography (2D-CEUS) and 3D-CEUS were used to assess 30 patients including living donor candidates and patients with upper abdomen tumors.The reference standard was operation or CTA or DSA or MRA,and the accuracy for detecting hepatic artery variants provided by the two methods was evaluated.Arterial anatomic types were defined by using Michels classification.Results The total accuracy for detecting hepatic artery anatomy types by 2D-CEUS was 40.0% (12/30),while 83.3% (25/30) by 2D-CEUS.For convention anatomy types the accuracy on 2D-CEUS and 3D-CEUS were 40.9%(9/22)and 90.9%(20/22),respectively.The difference was statistically significant (P<0.05).For anatomy variants types the accuracy on 2D-CEUS and 3D-CEUS were 37.5%(3/8)and 62.5%(5/8),respectively.No significant difference between these two methods was observed.Conclusion 3D-CEUS was a new method in diagnosis of hepatic arteries anatomy types with practical clinical value in evaluation of the living liver donors.

Objective To assess the feasibility of three-dimensional contrast-enhanced ultrasonic cholangiography(3D-CEUSC) in cadaver liver.Methods The 3D-CEUSC was performed in 6 cases of cadaver liver.Image quality of 3D-CEUSC was evaluated.The visualization of branching orders,the degree of visibility and coincidence of morphous were compared with those of cholangiagraphy using fluoroscopy.Results The imaging quality of 3D-CEUSC was inferior to that of cholangiography with significant difference.The three-dimensional biliary tree structures were visualized in all 6 3D-CEUSC.The maximum visualization of branching orders in 3D-CEUSC was (3.67±0.52),which was equal to the results(4.00±0.63)by cholangiography (P=0.465).The degrees of visibility of biliary tree were equivalent with those by cholangiography in the first and second order with significant difference.The coincidence of morphous was excellent compared the images of 3D-CEUSC with direct X-ray cholangiography.Conclusion 3D-CEUSC is a new technique as a useful supplement to cholangiography in evaluation of biliary anatomy and variation before graft harvesting in LDLT.

Adult ; Aged ; Coal Mining ; Health Promotion ; methods ; Humans ; Male ; Middle Aged ; Occupational Health ; statistics & numerical data ; Young Adult

Objective:To compare the short-term effects of hip muscles strengthening and quadriceps strengthening on knee osteoarthritis (KOA), and discuss the advantages of hip muscles strengthening. Methods:From October, 2015 to May, 2016, 42 old females with KOA were divided into two groups equally. They received hip strengthening (HS group) and quadriceps strengthening (QS group) for two weeks, respectively. The pain, stiffness and physical function scores of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured. Isokinetic strength peak torque (PT) was assessed for knee extensors and flexors, and 6-minute Walk Test was also evaluated. They were followed up two months later. Results:Before exercise, there was no significant difference in all the indexes between two groups (P > 0.05). Two weeks after exercise, the knee flexor PT (t = -4.038, P = 0.001) and 6-minute walk distance (t = -2.474, P = 0.022) increased in QS group; the pain, stiffness and physical function scores of WOMAC (t > 2.487, P < 0.05), the knee extensor and flexor PT (|t| > 6.370, P < 0.001), and 6-minute walk distance (t = -2.241, P = 0.037) improved in HS group; the scores of WOMAC were lower (t > 2.087, P < 0.05) and the knee extensor PT was higher (t = -5.028, P < 0.001) in HS group than in QS group. At two-months' follow-up, the drop-out rate was significantly lower in HS group than in QS group (χ² = 13.480, P < 0.001). Conclusion:Hip muscles strengthening is a good choice for KOA in the early stage of treatment, which could avoid the pain in quadriceps training, increase quadriceps strength and improve physical function.

To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.
Adult ; Cytochrome P-450 CYP2D6 ; physiology ; Humans ; Isoxazoles ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Paliperidone Palmitate ; Pyrimidines ; pharmacokinetics ; Risperidone ; pharmacokinetics