Advances in research on the impact of the plateau environmental on the drug metabolism / 药学实践杂志

Plateau environment will affect the metabolism of drugs in the body, which will cause changes in pharmacokinetic parameters, expression and function of drug metabolizing enzymes and transporters. With the rapid development of the pharmaceutical industry, therapeutic drug monitoring (TDM) has been widely paid attention to as a basis for personalized drugs. What impact does the plateau environment on monitoring drugs? In this literature review, we will summarize the types of commonly used therapeutic monitoring drugs, therapeutic windows, and blood samples, analyze the effects of plateau hypoxic environment on the metabolism of commonly used monitoring drugs, provide a reference for the clinical treatment and monitoring drugs of plateau, better ensure the rational use of drugs in the plateau population, and also provide a reference for the later research group to conduct the monitoring of plateau therapeutic drugs and the selection of research drugs.

Therapeutic window analysis of Tripterygium wilfordii processed by liquorice: an instantiation using allergic contact dermatitis / 中国中药杂志

The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.

Causas de no trombólisis: en pacientes en ventana terapéutica con accidente cerebrovascular isquémico atendidos en Hospital Herminda Martín de Chillán / Causes of non-thrombolysis in patients in therapeutic window with ischemic stroke treated in Hospital Herminda Martín de Chillán

INTRODUCCIÓN: El ataque cerebro vascular (ACV) es una emergencia médica, que ocurre cuando se interrumpe el suministro de sangre al cerebro o cuando existe un sangrado en el cerebro. EL OBJETIVO de esta investigación fue determinar las causas de la no trombolisis en pacientes con ventana terapéutica en accidente cerebral isquémico. MATERIALES Y MÉTODOS: Se realizó un estudio descriptivo con el fin de conocer el argumento de no utilización de tratamiento trombolítico en pacientes dentro de ventana terapéutica en accidente cerebral isquémico que consultaron o fueron derivados al Hospital Clínico Herminda Martín de Chillán, desde octubre de 2017 a marzo de 2018. Se revisaron las fichas clínicas tanto de pacientes egresados vivos como fallecidos. Estas se obtuvieron del Servicio de Neurología, extrayendo la información de Datos de Atención de Urgencias (DAU) y/o ficha clínica. RESULTADOS: Una muestra de 78 pacientes cumplió con los criterios de inclusión del estudio, cuya principal causa de no trombolisis en ventana terapéutica fue presentar un puntaje en la escala de NIHSS menor a 5 puntos, representando el 20,51% del total. DISCUSIÓN: Según la literatura, los principales motivos de exclusión en este grupo de pacientes fueron los ACV con manifestaciones leves (13,1%), mejoría clínica (18,2%) y exclusiones percibidas en el protocolo (13,6%), los cuales coinciden con esta investigación, donde el principal motivo fue un puntaje de NIHSS < 5, manifestando déficit neurológico leve al ingreso. Se recomienda la inclusión del criterio de funcionalidad previa a terapia trombolítica, en este grupo de pacientes. En pacientes en ventana terapéutica con accidente cerebrovascular isquémico atendidos en Hospital Herminda Martín de Chillán.

INTRODUCTION: Vascular brain attack (CVA) is a medical emergency, which occurs when the blood supply to the brain is interrupted or when there is bleeding in the brain. The OBJECTIVE of this research was to determine the causes of non-thrombolysis in patients with therapeutic windows in ischemic stroke. MATERIALS AND METHODS: A descriptive study was carried out in order to know the argument of non-use of thrombolytic treatment in patients with therapeutic window in ischemic stroke who consulted or was referred to the Hospital Clínico Herminda Martín de Chillán Clinical, from October 2017 to March of 2018. The clinical records of both living and deceased patients were reviewed. These were obtained from the Neurology Service, extracting the information from Emergency Care Data (DAU) and / or clinical record. RESULTS: A sample of 78 patients met the inclusion criteria of the study, whose main cause of non-thrombolysis in the therapeutic window was to present a score on the NIHSS scale of less than 5 points, representing 20.51% of the total. DISCUSSION: According to the literature, the main reasons for exclusion in this group of patients were stroke with mild manifestations (13.1%), clinical improvement (18.2%) and perceived exclusions in the protocol (13.6%), which, coincide with this investigation where the main reason was an NIHSS score <5, manifesting mild neurological deficit upon admission. The inclusion of the functionality criterion prior to thrombolytic therapy is recommended in this group of patients.

Developing an integrated model of toxicity and efficacy of Chinese medicine based on supramolecular “imprinting template” analysis / 药学学报

Chinese material medica (CMM) is the foundation for treating disease using traditional Chinese medicine (TCM), which is not only guided by the basic theory of TCM but also follows the general rules of drug action. There are both toxicity and efficacy in TCM. For TCM the integrated regularities of its toxicity and efficacy were demonstrated in their prescription, which were qualitatively characterized by compatible experiences such as "seven emotions", "Yin" and "Yang" compatibility, etc. When the toxicity is still produced by oral administration according to the prescription of TCM theory or administration is not abided by original requirement, the integral regularities of toxicity and efficacy that depends on experience appears to be at a loss what to do. Especially in recent years, with the modernization of TCM and the continuous advantages in new medicinal innovation, the CMM safety incidents occurred frequently. It is very urgent for us how to establish a set of integrated methods that are adequately situated to multiple components for TCM. With the combination of the biological supramolecular chemistry and the basic theory of TCM, an integrated model of toxicity and efficacy based on TCM supramolecular "imprinting template" has begun to take shape. The CMM and the human body are both biological supramolecular bodies that follow the autonomic action rules of their "imprinting template". The integrated trends of toxicity and efficacy are able to build on systematical results of single components in CMM based on the theory of TCM to treat diseases by prescription on syndromes. It is also the systematic actions resulting from single effective components in CMM by the supramolecular "imprinting template" self-acted regularities. Through the qualitative and quantitative analysis of supramolecular "imprinting templates" characteristics and actions and their network chromatotoxicometrology (chromatopharmacometrology), a toxic and effective integrated analysis methods will be established on an integrated "therapeutic window" for components in the CMM. This effort will finally permit the description of the components of the pharmacokinetic overlaid law of "therapeutic window", plotted to lower-overflow, entering and higher-overflow profiles.

Result Analysis of 2 608 Samples of Serum Concentration for Valproate and Carbamazepine / 中国药师

Objective: To analyze the serum concentration results of sodium valproate (VPA) and carbamazepine (CBZ) and explore the relationship between the serum concentration and age, clinical efficacy and adverse reactions to provide reference for the rational clinical use.Methods: Retrospective analysis was used to collect the clinical data of the patients from March 2015 to March 2016, including gender, age, clinical diagnosis, medication, usage and dosage, the last medication time, sampling time, blood concentration and the other related data, and the data were compared and analyzed.Results: Totally 2608 samples were collected, including 2 205 ones for VPA and 403 ones for CBZ.Totally 1 123 cases (50.93%) of VPA and 292 cases (72.46%) of CBZ were within the range of therapeutic windows.In the 2 205 cases of VPA, 1 814 cases (82.27%) were with single drug treatment, and the serum concentration lower than the lower limit of therapeutic window accounted for 790 cases (43.55%) with the effective rate of 43.55% for epilepsy.The serum concentration within the range of therapeutic window accounted for 921 cases (50.77%) with the effective rate of 88.27% for epilepsy, and that higher than the higher limit of therapeutic window accounted for 103 cases (5.68%) with the effective rate of 81.55%.As for CBZ, the number was 58 cases (22.39%) with the effective rate of 48.28%, 195 cases (72.29%) with the effective rate of 79.49% and 6 cases (2.32%) with the effective rate of 83.34%, respectively.Totally 391 cases (87.21%) of VPA combined with the other antiepileptic drugs, such as levetiracetam and lamotrigine.The effect of age on the serum concentration of VPA and CBZ was significant (P<0.05).Conclusion: There are great individual differences in serum concentration of VPA and CBZ among patients.The therapeutic effect and adverse reactions of VPA and CBZ are closely related to the serum concentration.Monitoring the serum concentrations may provide evidence for the rational administration and plays an important role in the treatment of epilepsy.

Protection of Diterpene Ginkgolides Meglumine Injection on acute injury of ischemic stroke in rats / 药物评价研究

Objective To investigate the protective effect and therapeutic window of DGMI on ischemic stroke in rats,and to explore the related mechanism.Method The rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by 72 h of reperfusion.DGMI (i.p.,1.25,2.5,5.0,and 10.0 mg/kg,Bid) was administered at 1 h after the onset of ischemia.Neurological score was evaluated after 24 and 72 h of reperfusion rcspectively.In fact volume,cerebral water content,oxidative stress markers,and IL-1β were evaluated after 72 h of reperfusion.The rats were treated with DGMI 5.0 mg/kg 0.5 h before reperfusion or 1 h,2 h,3 h,and 6 h after reperfusion to determined therapeutic window.Result Treatment with DGMI (2.5,5.0 mg/kg) significantly ameliorated neurological deficit,infarct volume and cerebral water content after cerebral ischemia reperfusion.DGMI also reduced the content of malonaldehyde (MDA),IL-1β,down-regulated the activities of creatine kinase (CK),lacticdehydrogenase (LDH),and up-regulated the activities of superoxide dISmutase (SOD).Treatment with DGMI 5.0 mg/kg exhibited protective effects when administered at all time points except for 6 h after reperfusion.Conclusion DGMI plays a certain protective role in ischemic stroke of rats,and the effect may be related to the improvement on the antioxidant capacity of brain tissue and the inhibition of overproduction of inflammatory cytokine.Moreover,the therapeutic window of DGMI isless than 6 h after reperfusion.

Tratamiento trombolítico del ictus isquémico agudo / Thrombolytic therapy of the ischemic stroke

El tratamiento trombolítico ha producido un cambio positivo en la actitud de los clínicos ante los pacientes con ictus isquémico agudo. Un modesto beneficio de un 13% contrasta con un aumento del 10% en la ocurrencia de hemorragia intracerebral sintomática. Sin embargo, la mortalidad no es diferente entre los pacientes que reciben el agente trombolítico rt-PA y los que reciben placebo. Se continua estudiando la ventana terapéutica extendida actualmente hasta 4,5 horas de iniciado el evento y la organización de la atención que permita beneficiar a un mayor número de pacientes, pues por varias razones solo son elegibles en promedio 3%. Se revisan los estudios más relevantes sobre la trombólisis especialmente intravenosa: el NINDS, el ECAS III, el IST-3 y el DIDAS y DEDAS. Se describen las principales complicaciones de este tipo de terapia: la hemorragia intracerebral sintomática, otros tipos de hemorragias, angioedema y ruptura miocárdica

Thrombolytic therapy has positively changed the attitude of clinicians to treat patients with acute ischemic stroke. Treated patients were 13% more likely to achieve a recover with no significant disability after 3 month. This benefit was achieved at the cost of a 10% increase in the rate of symptomatic intracranial hemorrhage. However, this increase did not result in a higher rate of death or severe disability in the treated group. Intravenous rt-PA can be given with significant but decreasing benefit and an acceptable risk to benefit ratio up to 4,5 hours as therapeutic window. Thrombolytic therapy remains substantially underused. Most relevant trials which deal with thrombolytic therapy: NINDS, ECAS III, IST-3, DIDAS andDEDAS, are analyzed. The most frequent complications of this therapy are described

Neuroprotection of mild brain hypothermia against cerebral ischemic injury / 中华物理医学与康复杂志

Objective To study the effect of mild brain hyothermia on cerebral ischemic injury. Methods Global cerebral ischemia was established by modified Pulsinelli 4-vessel occlusion model. Forty-eight Sprague-Dawley rats were divided into 4 group: a sham-operated group, a normothermia (37～38℃) ischemic group and a mild is-chemic hypothermia (31～32℃) group; the mild ischemic hypothermia was subdivided into 4 groups with the hypo-thermia lasting for 30 min, 60 min, 120 min and 240 min, respectively. After 240 rain of reperfusion following 20 min cerebral ischemia, the levels of nitric oxide products nitrite (NO2) ,endothelin-1 (ET1) , tumor necrosis fac-tor alpha (TNFα) and interleukin-1 beta (IL-1β) in brain tissue and the lactate dehydrogenase (LDH), aspartate aminotransferase(AST) , creatine kinase(CK) and its brain band isoenzyme (CK-BB) in plasma were measured. Results The levels of IL-1β,TNFα, ET1 and NO2. in brain tissue, and the amounts of LDH, AST, CK and CK-BB in serum were higher in normothermia ischemic group than those in sham-operated group (P <0.05). Mild hypother-mia lasting for 60 min to 240 min markedly decreased the levels of IL-1β, TNF-α, ET1 and NO2 in brain tissue, and the amounts of LDH, AST, CK and CK-BB in serum in normothermia ischemic group, when compared with normo-thermia ischemic group (P < 0.05 or P < 0.01). Mild hypothermia lasting for 30 min did not influence the content of IL-1β, TNF-α, ET1 and NO2 in brain tissue when compared with normothermia isehemia group (P > 0.05). Con-clusion Mild brain hypothermia post-ischemia can significantly suppress the inflammation response in ischemic brain tissue and stabilize the function of cell membrane. The best neuroprotection of mild brain hypothermia must be carried out immediately and last for more than 60 minutes.

Therapeutic Window Concentration of Tacrolimus: Survey of 56 Cases of Renal Transplant Recipients / 中国药房

OBJECTIVE: To explore the therapeutic window concentration of tacrolimus(FK506) suitable for Chinese renal transplant recipients. METHODS: The whole blood valley concentration level in 56 renal transplant recipients 12h after oral administration with FK506 was determined by MEIA (Microparticle Enzyme Immunization). The rejections and the renal toxic reaction were observed as well. RESULTS: The recommended therapeutic window concentration of FK506 for Chinese renal transplant recipients were the following: 9～14?g/L during the first month; 8～12?g/L during the second to the third month; 6～10?g/L during the fourth to the sixth month; 4～6?g/L during the seventh to the twelfth month. CONCLUSION: FK506 has a satisfactory immune suppression effect while reducing incidences of rejections and renal toxic reactions if used within the above therapeutic window concentration.

Discussion on Therapeutic Window Concentration of Digoxin / 中国药房

0.05),the toxi?cation rate of the low dose group was lower than that of the routine group(P0.05),the effective concentration of the low dose digoxin group was significantly lower than the routine group(P

Therapeutic window of hyperbaric oxygenation for acute cerebral infarction / 中华物理医学与康复杂志

Objective To study the influence of different starting time of hyperbaric oxygenation (HBO)therapy on acute cerebral infarction patients.Methods A total of 120 patients with first-time acute cerebral infarction were randomly and evenly divided into 4 groups:groups A,B,C and D.All the patients were treated with routine clinical regime.In addition,the patients in groups A,B andC started with HBO within 24 hours,between 24 and 72 hours and after 72 hours post-onset of the disease,respectively,while those in group D without HBO.All the patients were evaluated in terms of their neurological function and their perform- ante in activities of daily living,using the National Institutes of Health stroke survey(NIHSS)and Barthel In- dex(BI).Results At 14,28 and 90 davs after treatment,the patients in group A scored significantly better with NIHSS and BI than those in groups B,C and D(P0.05).No serious adverse reaction was found in the four groups.Conclusion The earlier the HBO therapy was started, the better the treatment.There will be no significant effects of HBO if it was started after 72 hours pust-onset of the disease.HBO therapy appears safe.

Analysis of 1812 Cases of Cyclosporine Therapeutic Drug Monitoring Data / 中国药房

OBJECTIVE:To evaluate1812cases of therapeutic drug monitoring(TDM)and the clinical drug utilization of cyclosporine.METHODS:Analysis and statistics of cyclosporine TDM data of1812cases(502subjects)in our hospital were carried out.RESULTS:Among all the1st TDM concentration,only41.4%was within the therapeutic window.Constituent ratios of patients whose drug concentration were monitored once,twice,or three times respectively was44.8%,16.3%and11.6%respectively.Among all the subjects undergoing3～4times of TDM,constituent ratio of patients whose drug con-centrations of the1st,2nd,3rd and4th TDM are within therapeutic window are40.6%,48.0%,50.0%and57.9%respec-tively.CONCLUSION:Although TDM is widely used,for some reasons,the constituent ratio of drug concentration within therapeutic window is low and the TDM times are much less than enough.Even TDM is multiple,the status of is not satisfac-tory,So clinics should pay more attention to the phenomenon that the patients’medication can’t be adjusted properly;Mean-while,it correlates with the expensive medication costs,etc.

Monitoring of Peak Blood Concentration in Renal Transplant Recipients 2h after Oral Administration of Cyclosporine A and Study on Therapeutic Window Concentration / 中国药房

OBJECTIVE:To study the therapeutic window of peak blood concentration at different time in domestic renal transplant recipients2h after administration with cyclosporine A(CsA).METHODS:The valley bottom levels(C 0 )and the peak levels(C 2 )were determined simultaneously by fluorescence polarization immunoassay(FPIA)in92patients2h after oral administration with CsA,the rejection and the hepatic and renal drug toxicities were observed.RESULTS:The recommended therapeutic window concentration of CsA(C 2 )in Chinese renal transplant recipients was1000～1300?g/L within the first month,950～1250?g/L within the second to third month,900～1100?g/L within the fourth to sixth month,750～1000?g/L within the seventh to twelfth month,600～800?g/L from the twelfth month after renal transplantation.CONCLUSION:Within the above therapeutic window concentration range,CsA is of ideal immuno-suppressive action meanwhile it can less rejection and minimize the hepatic and renal drug toxicities.