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AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.
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Objective To investigate the correlation between the features of multimodal magnetic resonance imaging (MRI) and the expression of human epidermal growth factor receptor-2 (HER-2) in ductal carcinoma in situ (DCIS). Methods A total of 53 patients with DCIS confirmed by surgery and pathology in Dezhou Second People’s Hospital from September 2018 to June 2021 were analyzed retrospectively. The patients were divided into HER-2 positive group (29 cases) and HER-2 negative group (24 cases). MRI features were compared between the two groups. Results There were significant differences in the internal enhancement characteristics, microvascular sign, and time-intensity curve type between the two groups (P < 0.05). There were no significant differences in lesion morphology, non-mass-like enhancement pattern, and apparent diffusion coefficient value (P > 0.05). The HER-2 positive group showed clumped enhancement (65.5%), type Ⅱ (48.1%) andtype Ⅲ (29.6%) time-intensity curves, and microvascular sign (89.7%). The HER-2 negative group showed clusteredring enhancement (50.0%), type Ⅱ (45.8%) and type I (54.2%) time-intensity curves, and microvascular sign (54.2%). A combination of clumped enhancement, microvascular sign, and type Ⅲ time-intensity curve showed 100% specificity and 100% positive predictive value for the diagnosis of HER-2 positive DCIS. Conclusion Clumped enhancement, microvascular sign, and type Ⅱ or Ⅲ time-intensity curve on MRI can largely reflect the expression of HER-2 in DCIS. The three can be used in combination to improve the diagnostic efficiency of HER-2 positive DCIS.
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Objective · To investigate the effect of metformin on insulin resistance (IR)-related metabolic parameters in olanzapine-bearing rats.Methods · Thirty female SD rats were randomly divided into metformin intervention group, olanzapine group and control group. During the first 6 weeks,5 mg /(kg·d) olanzapine was given to the two test groups . The control group was given the same amount of saline. From the 7th week, the intervention group began to combine with metformin 500 mg / (kg·d), while the olanzapine group combined with the same amount of saline, continuing for 4 weeks.At the end of 6th week and 10th week, intraperitoneal glucose tolerance and homeostasis model assessment IR index were assessed. Results · The area under the glucose tolerance curve (P=0.040) and the IR index (P=0.000) were significantly higher for the intervention group and the olanzapine group than the control group at the end of 6th week. At the 10th weekend, the glucose tolerance (P=0.015) and IR index in the intervention group were significantly lower than those in the olanzapine group (P=0.001). Conclusion · Metformin may rectify the impaired glucose tolerance and improve IR induced by olanzapine partly.
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Objective To explore the relationships between neuronal nicotinic acetylcholine receptor subunit gene polymorphisms and type 2 diabetes in Chinese han schizophrenics.Methods Five single nucleotide polymorphisms(SNPs )of CHRNA3 (rs1317286),CHRNA4 (rs1044396),CHRNA 7 (rs6494212) and CHRNA5 (rs16969968,rs684513) gene were analyzed in a sample of 346 schizophrenics with type 2 diabetes and 360 schizophrenics without type 2 diabetes.The five markers were genotyped by the TaqMan fluorogenic detection method with the ABI7900.Results There were no significant differences in alleles and genotypes distribution of the five genes between two groups (P＞0.05).For the CHRNA 7(rs6494212),there were significant difference in genotypes (P=0.039) and alleles distribution (P＜0.021) between two groups in male patients.The haplotypes constructed by markers of CHRNA5 were not associated with the 2 diabetes in Chinese Han male schizophrenics.The interaction analysis revealed a significant association between models made up by rs1317286,rs1044396,rs6494212,rs684513and 2 diabetes in Chinese Han male schizophrenics (P=0.002).Conclusion The CHRNA7(rs6494212) gene may be one of common susceptible genes for 2 diabetes in Chinese Han male schizophrenics.There is a significant association between models made up by rs131726rs1044396,rs6494212,rs684513 and schizophrenics with type 2 diabetes.
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Objective To explore the relationships between neuronal nicotinic acetylcholine receptor subunit gene polymorphisms and type 2 diabetes in Chinese han schizophrenics.Methods Five single nucleotide polymorphisms(SNPs )of CHRNA3 (rs1317286),CHRNA4 (rs1044396),CHRNA 7 (rs6494212) and CHRNA5 (rs16969968,rs684513) gene were analyzed in a sample of 346 schizophrenics with type 2 diabetes and 360 schizophrenics without type 2 diabetes.The five markers were genotyped by the TaqMan fluorogenic detection method with the ABI7900.Results There were no significant differences in alleles and genotypes distribution of the five genes between two groups (P＞0.05).For the CHRNA 7(rs6494212),there were significant difference in genotypes (P=0.039) and alleles distribution (P＜0.021) between two groups in male patients.The haplotypes constructed by markers of CHRNA5 were not associated with the 2 diabetes in Chinese Han male schizophrenics.The interaction analysis revealed a significant association between models made up by rs1317286,rs1044396,rs6494212,rs684513and 2 diabetes in Chinese Han male schizophrenics (P=0.002).Conclusion The CHRNA7(rs6494212) gene may be one of common susceptible genes for 2 diabetes in Chinese Han male schizophrenics.There is a significant association between models made up by rs131726rs1044396,rs6494212,rs684513 and schizophrenics with type 2 diabetes.
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Capacity assessment is of significant priority for medical treatment and clinical research invol-ving mental disorder patients,as to protect an individual's fundamental rights.Clinical judgment of individual's ca-pacity to consent most focus on medical situation,well-designed capacity assessment instruments should be used to support experienced clinical judgment.Capacity to consent can be adequately captured by measuring the constructs of understanding,appreciation,reasoning and communicating /expressing a choice.A large number of instruments designed by foreign developers to assess capacity to consent need validation and implementation in China,the in-strument designed by Chinese researchers has not been widely agreed.Establishing an effective capacity assessment instrument with psychometric properties (validity and reliability),which considering the clinical practice and culture background in china would be a breakthrough in methodology.
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OBJECTIVE: Duloxetine hydrochloride is a selective serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor. It is approved for effective treatment for major depressive disorder. The pharmacokinetics (PK) of duloxetine has been studied, but few pharmacokinetics properties in Chinese subjects are available. This study explored the dose proportionality and determined duloxetine levels in human plasma by comparing the PK properties after administration of single or multiple doses in healthy volunteers. METHODS: Thirty-six subjects were divided randomly into three groups and received a single dose of 15, 30, or 60 mg duloxetine. Those who received 30 mg continued on to the multiple-dose phase and received 30 mg daily for 7 days. Liquid chromatography/mass spectroscopy was applied to determine concentrations. The PK properties were calculated and included maximum plasma concentration (Cmax), time when maximum plasma concentration was reached (Tmax), time when half-maximum plasma concentration was reached (t1/2), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t), mean concentration levels (AUC0-infinity), and apparent total clearance of the drug from plasma after oral administration (CL/F). RESULTS: The standard calibration curve was linear in the concentration range 0.11-112 ng/ml (r>0.992). Linear PK properties were found at doses of 15-60 mg. The Cmax and AUC were proportional to dose, but the Tmax and t1/2 did not increase with increasing dose. CONCLUSION: No significant differences in the PK parameters were found among the three groups during the single-dose phase. The AUC and Cmax were greater in the multiple-dose phase, indicating duloxetine accumulation following multiple-dose administration.
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Humans , Administration, Oral , Area Under Curve , Asian People , Calibration , Depressive Disorder, Major , Norepinephrine , Plasma , Serotonin , Spectrum Analysis , Tablets, Enteric-Coated , Thiophenes , Duloxetine HydrochlorideABSTRACT
Objective To study the effects caused by novel antipsychotics quetiapine and aripiprazole on concentrations of platelet 5-HT in patients with schizophrenia,and to explore the relationships among the change of platelet 5-HT concentrations, psychiatric symptoms and the sensitivity of therapy. Methods Sixty-eight patients with schizophrenia meeting International Classification of Diseases-10 (ICD-10) were enrolled in the study. They were divided into quetiapine group(n=34) and aripiprazole group(n=34) according to the sequence of admis-sion. The platelet 5-HT concentrations were measured with high performance liquid chromatography method(HPLC-ECD). The positive and negative syndrome scale (PANSS) was used to evaluate the psychopathology. Treatment emergent symptom scale (TESS) was used to evaluate the side effects. PANSS,TESS were used at pre-treatment,the end of 4th and 8th week of treatment. Results The platelet 5-HT concentrations in two groups were higher af-ter 8 weeks treatment,but had no statistically significant difference (P>0.05). In quetiapine group, the platelet 5-HT concentration was (458.89±233.36) ng/10~9 at the pre-treatment, and (554.31±313.22) ng/10~9 at the end of treatment (t=1.709, P=0.099). In aripiprazole group, the platelet 5-HT concentration was (409.83±149.32)ng/10~9 at the pretreatment, and (421.27±245.96)ng/10~9 at the end of treatment (t=0.321, P=0.819). There was no difference between two groups(P>0.05). Stepwise regression analysis showed the changing rate of platelet 5-HT concentrations was positively correlated with the dosage of quetiapine (r=0.385, P=0.039).It was positively correlated with the decreasing rate of PANSS in aripiprazole group(r=0.391, P=0.040). Con-dusion The changes of psychiatric symptoms and the dosages of antipsychotics maybe have intimate relationships with platelet 5-HT concentrations in the course of medication.
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Objective To investigate the effect of risperidone on regional cerebral blood flow (rCBF) and the relationship between efficacy and rCBF ratio. Methods Twenty four naive schizophrenic patients (diagnosed according to the ICD 10) completed 8 weeks treatment with risperidone. Ten patients were male and 14 were female. Twenty six healthy controls were enrolled as control group. The treatment dose of risperidone was 3～6 mg/d. After 8 weeks treatment, brain imaging was conducted again. Results Before treatment with risperidone, compared to the control group, the baseline rCBF ratios of left and right inferior posterior temporal of patients were higher and the cognitive activated rCBF ratios of left mid-lateral frontal was lower. After treatment, the baseline state rCBF ratios of right lateral temporal, left and right superior posterior temporal were significantly decreased. The cognitive activated rCBF ratios of left and right inferior medial frontal, left inferior lateral frontal, left superior fronto temporal and left superior lateral fronal significantly increased. The efficacy was correlated with changes of the baseline rCBF ratio in some RIOs. Conclusions Risperidone could change the blood perfusion in some ROIs. It suggested that the perfusion in these ROIs could be useful for predicting treatment efficacy.