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1.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 171-177, 2022.
Artigo em Chinês | WPRIM | ID: wpr-1014894

RESUMO

AIM: To investigate the relationship between genotypes of rs628031, rs650284, rs683369 of SLC22A1 gene and the toxicities and clinical response of oxaliplatin in patients with colorectal cancer. METHODS: A total of 72 patients diagnosed as colorectal cancer during January 2018 to June 2018 were selected and all patients received oxaliplatin treatment. Their peripheral venous blood was collected and genotyping was conducted by using SNaPshot. The toxicities including gastrointestinal toxicity, hematological toxicity and peripheral neurotoxicity were evaluated according to the Common Terminology Criteria Adverse Events (CTCAE) Version 5.0. Clinical response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1). RESULTS: The results of Chi-test showed that different genotypes of SLC22A1 SNP sites rs628031 and rs683369 may be related to the toxicities and clinical response of oxaliplatin significantly. Specifically, when compared with the patients with GG type of rs628031, the patients with the GA or AA type had a lower incidence of grade 3 nausea and vomiting (P=0.017) and may also be less responsive to efficacy (P=0.008). When compared with the patients with CC type of rs683369, the patients with the GC or GG type had a lower incidence of grade 3 nausea and vomiting (P=0.002) and may also be less responsive to efficacy (P=0.014).CONCLUSION: The polymorphisms of SLC22A1 gene are closely related to the toxicities and clinical response of oxaliplatin in patients with colorectal cancer, which may be helpful for improving clinical treatment.

2.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 324-331, 2021.
Artigo em Chinês | WPRIM | ID: wpr-1015071

RESUMO

Epidemiological survey shows that the prevalence, incidence rate and symptoms of mental disorders are affected by sex. A large number of studies have shown that men and women respond differently to psychotropic drugs in clinical application. Moreover, some studies have shown that there are sex specific psychotropic drug use patterns in patients with depression. This paper summarizes the sex differences in pharmacokinetics of psychotropic drugs caused by physiological differences between men and women, and collates the current pharmacodynamic studies of mainstream clinical psychotropic drugs, with special attention to the effect of sex hormones on the therapeutic response of psychotropic drugs. This paper discusses the specific role and necessity of therapeutic drug monitoring in dealing with clinical sex differences in psychotropic drugs, hoping to provide reference for individual rational drug use.

3.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 1309-1319, 2021.
Artigo em Chinês | WPRIM | ID: wpr-1014949

RESUMO

Physiologically based pharmacokinetic (PB-PK) model simulates the circulation of blood flow in systemic organs by using mathematical model to quantitatively describe the behavior characteristics of drugs in the body. The application of PB-PK model to special population to predict the pharmacokinetic behavior of drugs in special populations can provide support for clinical rational drug use. In recent years, chronic liver disease has gradually become an important health problem. Due to the impairment of patients' liver function, the disposal process of drug in vivo will change to some extent. Therefore, it is necessary to evaluate the impact of liver dysfunction on the drug absorption, distribution, metabolism, elimination (ADME) in order to ensure the safety and effectiveness of drug use. PB-PK model can accurately determine the ADME process of drugs in patients according to the level of liver function, and play an important role in guiding clinical rational drug use. This review will start from the impact of liver function on the process of drug ADME, summarize and discuss how PB-PK model can build a model according to the physiological and pathological changes of patients with liver dysfunction for more accurate extrapolation prediction.

4.
China Journal of Chinese Materia Medica ; (24): 2789-2794, 2010.
Artigo em Chinês | WPRIM | ID: wpr-279353

RESUMO

Flavanoids are important phytochemistry compositions in foods and traditional Chinese medicines (TCM) and are mainly oxidized by CYP1A family in vivo. Some methoxyflavones could also be metabolized through demethylation. Usually, flavanoids own one or more phenolic hydroxyl group in their molecular structures, which facilitate conjugation with glucuronic acid and sulphuric acid, forming metabolites with good water-solubility to excrete. Natural flavanoids mainly exist in glycoside, and after oral ,they would be easily metabolized to aglycone by hydratase in gut microflora and then absorbed into blood. Besides, many flavanoids have strong inhibitory actions on Cytochrome P450 enzymes, which are significant mechanisms in cancer precaution and tumor inhibition. In this paper, we reviewed lots of articles and summarized metabolism characteristics of flavanoids and metabolism interaction with Cytochrome P450 enzymes.


Assuntos
Animais , Humanos , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450 , Metabolismo , Tratamento Farmacológico , Flavonoides , Metabolismo , Farmacologia , Usos Terapêuticos
5.
China Journal of Chinese Materia Medica ; (24): 1720-1723, 2009.
Artigo em Chinês | WPRIM | ID: wpr-344547

RESUMO

<p><b>OBJECTIVE</b>The aim of this study is to develop a simple and rapid HPLC method and investigate the effect of glycyrrhizin on pharmacokinetic fate of paeoniflorin after intravenous administration.</p><p><b>METHOD</b>Paeoniflorin and glycyrrhizin was administrated to rat via vena caudalis, and paeoniflorin in rat plasm was determined by RP HPLC method and internal standard method. All data were subsequently processed by the pharmacokinetic Software WinNonLin. The non-compartmental pharmacokinetic parameters of area under the plasma concentration-time curve (AUC/min x mg x L(-1)), clearance (CL/mL x min(-1) x kg(-1) ) and volume of distribution (Vd/mL x kg(-1)) were calculated based on moment methods.</p><p><b>RESULT</b>The values of AUC, V(d) and CL was 166.81 +/- 26.94, 394.33 +/- 29.52, 18.40 +/- 3.12 in control group, respectively; however, the values of AUC, V(d), CL was 235.44 +/- 46.48, 266.63 +/- 48.43 and 13.16 +/- 2.59 in experimental group.</p><p><b>CONCLUSION</b>Glycyrrhizin significantly influenced the pharmacokinetic fate of paeoniflorin, increasing the value of AUC and decreasing CL and V(d).</p>


Assuntos
Animais , Feminino , Masculino , Ratos , Benzoatos , Sangue , Farmacocinética , Hidrocarbonetos Aromáticos com Pontes , Sangue , Farmacocinética , Glucosídeos , Sangue , Farmacocinética , Ácido Glicirrízico , Injeções Intravenosas , Monoterpenos , Distribuição Aleatória , Ratos Sprague-Dawley
6.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 1163-1167, 2007.
Artigo em Chinês | WPRIM | ID: wpr-407637

RESUMO

AIM: To illustrate the effects of drug transporters on the bile efflux of ibuprofen glucuronide(IBG), the difference of bile excretion and plasma concentration of ibuprofen(IB) and its glucuronides was studied in EHBR and normal SD rat(SDR). METHODS: After 20 mg/kg of IB enantiomers administrated intravenously, the bile and blood were collected from the rats and the concentration of IB and their glucuronide were measured by HPLC methods. RESULTS: The bile excretion of IBG was obviously (but no totally) suppressed in EHBR (1.7%±1.0%, 0.6%±0.9% of the dose respectively for S-IBG and R-IBG) compared with that in SDR (18.4%±4.0% and 3.0%±2.4% of the dose respectively for S-IBG and R-IBG), for both kinds of rats, there are more S-IBG excreted than that of R-IBG. As the result of reduction of IBG excreted in bile, the concentration of IBG was higher in blood in EHBRs. CONCLUSION: The results suggest that Mrp2 is the most important transporter for IBG, and other transporter(s) may participate in the process.

7.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 1231-1236, 2007.
Artigo em Chinês | WPRIM | ID: wpr-407544

RESUMO

To establish an HPLC mehod for the analysis of pharmacokinetics of salvianolic acid B in rats. METHODS: The biological samples were extracted with acetic ether. The chromatographic conditions were as follows: Hypersil ODS column (200 mm×4.6 mm, 5μm) was used. The mobile phase was acetonitrile-water(with Ammoniom Acetate 0.25 mol/L) was set at 328 nm. RESULTS: Salvianolic acid B was injected intravenously at doses of 1.6, 3.2, 6.4 mg/kg. The terminal elimination half-life(t1/2) of α phase and β phase was (3.1±0.1) min and (31.5±3.2) min. The extents of excrement,urine and biliary excretion of salvianolic acid B were 1.43%±0.90%, 0.77%±1.01% and 8.82%±4.11%. The tissue concentration of salvianolic acid B was as followed in order: Cheart>Cliver>Clung>Cintestine>Ckidney>Cspleen>Cstomach. The plasma protein binding rate of salvianolic acid B in human plasma and in rat was similar(89.2%±1.8%,92.5%±1.5%). CONCLUSION: The method is accurate, stable and reliable, and can be used for the investigation of salvianolic acid B in pharmacokinetics research. Salvianolic acid B eliminates fast and it shows a high plasma protein binding rate, the mainly excretion way of salvianolic acid B is from biliary.

8.
Acta Nutrimenta Sinica ; (6)1956.
Artigo em Chinês | WPRIM | ID: wpr-676953

RESUMO

Potassium metabolism in young adult men exercising in the heat for six consecutive days and the effect of potassium deficiency in mice and rats induced by low potassium diet during heat exposure were observed. Increased potassium loss in sweat and lower potassium intake resulted in negative potassium balance. Individuals with a negative potassium balance had lower se- rum potassium levels and higher body temperature after exercise. Potassium deficient mice accomplished less work done (2.372 vs 4.253 Kg.M) but exih-ibited a markedly greater rate of heat gain (1.36 vs 0.87℃/Kg.M) as compared to the controls. The survival rate and cellular energy metabolism also decreasedThese observations suggest that prevention from potassium deficiency must be emphasized during prolonged physical activity under hot environments. According to the linear regression equations between potassium intake and balance, it is proposed that the potassium requirements in mild and medium physical activity in the heat are 40 and 60 mEq/day respectively, and the allowance of potassium in the latter may be 70-80 mEq/day.

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