In vitro models for neuropathic pain phenotypic screening in brain therapeutics.

The discovery of brain therapeutics faces a significant challenge due to the low translatability of preclinical results into clinical success. To address this gap, several efforts have been made to obtain more translatable neuronal models for phenotypic screening. These models allow the selection of active compounds without predetermined knowledge of drug targets. In this review, we present an overview of various existing models within the field, examining their strengths and limitations, particularly in the context of neuropathic pain research. We illustrate the usefulness of these models through a comparative review in three crucial areas: i) the development of novel phenotypic screening strategies specifically for neuropathic pain, ii) the validation of the models for both primary and secondary screening assays, and iii) the use of the models in target deconvolution processes.

Comparing the interactions of nitrendipine with lysozyme or human serum albumin and the effects of vitamin C and naringin on these interactions by spectroscopy and molecular docking methods.

The interactions between drugs and proteins play a pivotal role in determining the pharmacological effects and disposition of drugs within the human body. This study focuses on exploring the interaction between nitrendipine and lysozyme/human serum albumin. Spectroscopic analysis indicated a compound static quenching, indicative of the formation of stable complexes between the drug and proteins. The addition of vitamin C or naringin resulted in a decrease of the binding constant between nitrendipine and lysozyme/human serum albumin. The presence of these compounds may disrupt the interactions between the drug and proteins, potentially leading to an increased concentration of free nitrendipine in the bloodstream. Nitrendipine binds more easily to human serum albumin at 310 K, and human serum albumin has an average binding site ratio with nitrendipine approximately 0.1 higher than that with lysozyme. Vitamin C has a greater impact on the binding constant of nitrendipine to human serum albumin and lysozyme. Compared to the binary system of proteins with the drug, the ternary system with the addition of vitamin C at 310 K reduces the binding constants of lysozyme and human serum albumin by 85%. In conclusion, this study explores the significance of considering drug-protein interactions in understanding drug behavior and potential drug-food interactions.

The development of a novel simultaneous in vitro dissolution - in situ perfusion system as a potential tool for studying the absorption of solid oral formulation in rat.

The aim of this work is to develop a novel simultaneous in vitro dissolution - in situ perfusion system (SDPS) as a potential tool to evaluate the in vivo performance of solid oral formulation in rat. The innovative nitrendipine (NTD) tablet of Bayotensin mite® made in Germany was used as reference listed drug (RLD), and five generic products from Chinese market were compared with RLD using the in vitro dissolution test method specified by the orange book and the SDPS method developed in this study. Four self-prepared NTD tablets with different proportions of microcrystalline cellulose/starch were employed to investigate the discriminatory ability of the SDPS for formulation. In addition, the predictivity of the SDPS in relation to data from in vivo pharmaceutics studies was evaluated. The 45-min dissolution test and multiple-pH dissolution profiles of generic product 1 and 2 have no difference compared with the RLD, but their dissolution profiles from the SDPS showed statistically significant differences. A biexponential formula successfully described the concentration profiles of self-prepared formulations in SDPS experiments. The kdis (0.08 ± 0.01 ∼ 0.2 ± 0.03 min-1) and ka (about 2.30 × 10-3 min-1) values calculated by the formulas of F1-F3 suggested that the used excipients had no effect on the intestinal absorption of NTD, and it might be the property of active pharmaceutical ingredient that led to the difference among the generics. Furthermore, the in vivo rat pharmacokinetics study results of F1-F3 showed a good correlation (R2 = 0.99) with the SDPS data. In summary, the SDPS is a promising tool to detect the unexpected quality changes of pharmaceutical products in weakly regulated markets, facilitate formulation screening, and potentially reduce animal testing for estimating the in vivo absorption behavior of solid oral formulations. The absorption performance of generic drugs in vivo should be further investigated.

Photodegradation profiling of nitrendipine: evaluation of active pharmaceutical ingredient, tablets and its altered forms.

Nitrendipine (NTR) is a dihydropyridine drug, which is well-known as a photodegradable pharmaceutical. However, the photochemical reaction of NTR has not been evaluated in detail from now. In this study, we perform the photodegradation profiling of NTR for the elucidation of its photochemical behavior. NTR amounts during ultraviolet light (UV) irradiation were monitored using high performance liquid chromatography (HPLC). NTR was photodegraded almost completely within 24 h along with the generation of some photoproducts. Structural determination of two NTR photoproducts were carried out by means of electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). Obtained results from this study clarified one novel NTR photoproduct, a nitroso pyridine analogue, in addition to a pyridine analogue. Furthermore, photodegradation pathway of NTR was speculated based on chemical structures of NTR photoproducts to clarify its photochemical behavior. It was proposed that a singlet oxygen molecule might withdraw two hydrogen radicals resulting in the form of a pyridine analogue, and the following reduction of its nitro group might produce a nitroso pyridine analogue. Finally, we evaluated the photostability of NTR tablets and its altered forms, indicating that the change of the dosage form led to a decrease of the photostability of NTR tablets. The obtained results will be helpful for the additional research to evaluate the effect of NTR photodegradation on its own biological activities.

Formulation, Optimization and Evaluation of Nanoparticulate Oral Fast Dissolving Film Dosage Form of Nitrendipine.

The primary objective of the present research work was to develop nanoparticles incorporating (nanoparticulate) fast dissolving (orodispersible) film evincing enhanced solubility and bioavailability of nitrendipine (NIT). An antisolvent sonoprecipitation method was employed to produce the NIT nanosuspension (NS), which was optimized using the 32 optimal response surface design and then the optimized one was evaluated for various parameters (Gandhi et al., AAPS PharmSciTech 22 (1):1-15, 2021). The NIT nanoparticulate orodispersible film (N-ODF) was prepared utilizing the nanosuspension by the solvent casting method using the Vijay film-forming instrument. The N-ODF was optimized by the 23 full factorial design and was evaluated for several parameters. The optimized NS depicted a particle size of 505.74 ± 15.48 nm with a polydispersity index (PDI) of 0.083 ± 0.006 (Fig. 1b). The NIT nanoparticles showed a striking increment in saturation solubility (26.14 times), when compared with plain NIT (2). The developed NIT N-ODF exhibited thickness (0.148 ± 0.008 mm), folding endurance (280.33 ± 5.51 times), surface pH (6.86 ± 0.05), tensile strength (8.25 ± 0.13 kg/cm2), % elongation (63.5 ± 1.97%), and disintegration time (24.60 ± 1.31 s) to be within the standard intended limit. The in vitro dissolution study unveiled 100.28 ± 2.64% and 100.68 ± 2.50% of NIT release from lyophilized nanocrystals (in 8 min) and N-ODF (in 3.5 min), respectively, whereas the conventional NIT tablet took 30 min to release 99.94 ± 1.57% of NIT (Gandhi et al., AAPS PharmSciTech 22 (1):1-15, 2021). The in vivo pharmacokinetic study in rabbits inferred the achievement of significantly (p < 0.05) higher bioavailability of NIT on release from N-ODF in comparison to the conventional NIT tablet. Thus, the generation of N-ODF can be considered as a propitious move toward improving the efficacy of NIT to treat hypertension and angina pectoris.

Nitrendipine-Treatment Increases Cork Spot Disorder Incidence in Pear 'Akituki' (Pyrus pyrifolia Nakai.) by Altering Calcium Distribution Inside the Fruit.

'Akituki' (Pyrus pyrifolia Nakai.) is a very popular and profitable pear cultivar in China. However, its high susceptibility to cork spot disorder has limited its expansion of cultivated area. The mechanisms of cork spot disorder have been discussed extensively, focusing on Ca2+ deficiency, yet no consensus has been made. In this study, we applied nitrendipine (NI) as a Ca2+ uptake inhibitor to explore the role of calcium in cork spot disorder occurrence. Results showed that NI treatment on the fruit remarkably increased the incidence of cork spot disorder; alteration of mineral contents happened at the early developmental stage of the fruit, especially on the outer flesh and the peel of the fruit; and this gap was filled gradually along with the expansion of the fruit. Significant differences in the expression levels of Ca2+ transport-related genes were found in the inner flesh, outer flesh and peel during the fruit growth period. The observation of free Ca2+ localization indicated the intracellular imbalance of Ca2+ in the NI-treated fruit. In conclusion, NI treatment reduced the calcium content in the fruit at an early developmental stage, altered the related expression of genes and influenced the cellular Ca2+ balance in the fruit, which prompted the occurrence of cork spot disorder. Measures for the prevention and control of cork spot disorder should be taken at the early stage of the fruit development in the field.

Development of Nanonized Nitrendipine and Its Transformation into Nanoparticulate Oral Fast Dissolving Drug Delivery System.

The present research focuses on the development of a nanoparticulate (nanocrystals-loaded) rapidly dissolving (orodispersible) tablet with improved solubility and bioavailability. The nanosuspension (NS) was prepared by antisolvent sonoprecipitation technique and the optimized NS was lyophilized to obtain nanocrystals (NCs), which were evaluated for various parameters. The nitrendipine (NIT) nanoparticulate orodispersible tablet (N-ODT) was prepared by direct compression method. The optimized N-ODT was evaluated for pre and post compression characteristics, in vivo pharmacokinetic and stability profile. The optimized NS showed a particle size of 505.74 ± 15.48 nm with a polydispersity index (PDI) of 0.083 ± 0.006. The % NIT content in the NCs was found to be 78.4 ± 2.3%. The saturation solubility of NIT was increased remarkably (26.14 times) in comparison to plain NIT, post NCs development. The DSC and p-XRD analysis of NCs revealed the perseverance of the integrity and crystallinity of NIT on lyophilization. The results of micromeritic studies revealed the good flow-ability and compressibility of NCs blend. All the post-compression properties of N-ODT were observed within the standard intended limit. The dispersion, wetting, and disintegration time of the optimized batch of N-ODT was found to be 39 ± 1.13 s, 44.66 ± 1.52 s, and 33.91 ± 0.94 s respectively. The in vitro dissolution study displayed 100.28 ± 2.64% and 100.61 ± 3.3% of NIT released from NCs (in 8 min) and N-ODT (in 6 min) respectively, while conventional NIT tablet took 30 min to release 99.94 ± 1.57% of NIT. The in vivo pharmacokinetic study in rabbits demonstrated significantly (p < 0.05) higher bioavailability of NIT on release from N-ODT than the conventional NIT tablet. Thus, N-ODT could be a promising tool for improving the solubility and bioavailability of NIT and to treat cardiovascular diseases effectively.

Simultaneous determination of enalapril maleate and nitrendipine in tablets using spectrophotometric methods manipulating ratio spectra.

A fixed dose combination of enalapril maleate (EN) and nitrendipine (NT) achieved satisfactory blood pressure control rather than monotherapy. Four accurate spectrophotometric methods utilizing ratio spectra were developed and validated for the simultaneous determination of EN and NT in combined pharmaceutical dosage form (Eneas® tablets). The first method was first derivative ratio spectrophotometric method (1DD) where the amplitudes maxima were measured at 219.2 nm and 233.4 nm for the determination of EN and NT, respectively. The second method was ratio difference spectrophotometric method where EN and NT were estimated by measuring the amplitudes difference between 213 nm and 225 nm on the ratio spectrum of EN and between 241 nm and 227 nm on the ratio spectrum of NT. The third method was ratio subtraction followed by extended ratio subtraction, EN was determined at 210 nm by subtraction of the constant values from the ratio spectrum then multiplication with the divisor (NT spectrum). An extended ratio subtraction method was then applied in order to determine NT at 235 nm by using the zero-order spectrum of EN (10 µg/ml) as a divisor. The fourth method was ratio subtraction coupled with constant multiplication methods. The zero- order absorption spectrum of the laboratory prepared mixture was divided by NT (12 µg/ml) spectrum, subsequently, the value of the constant was multiplied by the divisor to obtain the original spectrum of NT, followed by its subtraction from the laboratory prepared mixture to get the spectrum of EN. EN and NT were determined at 210 nm and 235 nm, respectively. Linearity was ascertained over the concentration ranges of (1-11 µg/ml) for EN and (2-14 µg/ml) for NT, for the first and second methods and (2-13 µg/ml) for EN and (3-20 µg/ml) of NT, for the third and fourth methods. Application of the methods to the determination of the cited drugs in Eneas® tablets gave satisfactory results. Methods validation confirmed their accuracy and selectivity. Statistical comparison of the results with the reported one showed no significant difference, regarding precision and accuracy. Routine analysis of the cited drugs in quality control laboratories could be performed using the developed methods.

Biomimetic micellar mesoporous silica xerogel performs superior nitrendipine dissolution, systemic stability and cellular transmembrane transport.

To combine the advantages of micelles and biomimetic silica materials, biomimetic micellar mesoporous silica xerogel (BM-SX) was initially established, biomimetic silica xerogel (B-SX) was also studied as control and nitrendipine (NDP) was taken as model drug. The content mainly focused on drug dissolution, systemic stability and cellular transmembrane transport of NDP loaded B-SX and NDP loaded BM-SX. With extra mesopores formed due to HPMC E50 micelles, the mean pore diameter, surface area and pore volume of BM-SX were all larger than B-SX. After loading NDP into the two carriers, crystal NDP changed to amorphous phase, leading to enhanced NDP dissolution. BM-SX presented superior abilities not only for its higher drug dissolution compared to B-SX but also for its capacity in remaining high amorphous drug phase and therefore no drug dissolution reduction can be observed. The dynamic contact angle result confirmed the strong power of HPMC E50 micelles in maintaining amorphous NDP in the carrier to improve high systemic stability. Both B-SX and BM-SX could increase drug absorption permeability and exert function as drug efflux inhibitor to inhibit the efflux effect of p-gp drug pump and promote NDP absorption and transport, and BM-SX was superior owing to micelles in the system.

Validated LC-MS/MS method for the simultaneous determination of enalapril maleate, nitrendipine, hydrochlorothiazide, and their major metabolites in human plasma.

Hypertension is a major risk factor for atherosclerosis and ischemic heart disease. Most hypertensive patients need a combination of antihypertensive agents to achieve therapeutic goals. A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometric method was developed and validated for simultaneous determination of enalapril maleate (ENA) and its major metabolite enalaprilat (ENAT), nitrendipine (NIT) and its major metabolite dehydronitrendipine (DNIT), and hydrochlorothiazide (HCT) in human plasma using felodipine as an internal standard (IS). The drugs were extracted from plasma using one-step protein precipitation. Chromatographic separation was performed on a Symmetry C18 column, with water and acetonitrile (10:90, v/v) as mobile phase. The detection was carried out using multiple reaction monitoring mode and coupled with electrospray ionization source. Multiple reaction monitoring transitions were m/z 377.1 → 234.1 for ENA, m/z 349.2 → 206.1 for ENAT, m/z 361.2 → 315.1 for NIT, m/z 359 → 331 for DNIT, m/z 295.9 → 205.1 for HCT, and m/z 384.1 → 338 for felodipine (IS). The method was linear over concentration ranges of 1-200, 20-500, 5-200, 2-100, and 5-200 ng/mL for ENA, ENAT, NIT, DNIT, and HCT, respectively, with r2 ≥ 0.99. Method validation was performed according to U.S. Food and Drug Administration guidelines. The validated method showed good sensitivity and selectivity and could be applied for therapeutic drug monitoring and bioequivalence studies.

Development and optimization of nanoemulsion based gel for enhanced transdermal delivery of nitrendipine using box-behnken statistical design.

Objective: The purpose of present research was to develop and statistically optimize nitrendipine nanoemulsion gel for transdermal delivery using box-behnken statistical design.Method: The nanoemulsion formulations bearing nitrendipine were prepared by application of ternary phase diagram and spontaneous emulsification method. Box-behnken design was employed for the optimization of nitrendipine loaded nanoemulsion. The independent variables were oil, surfactant and co-surfactant while globule size, drug content and zeta potential were dependent variables. The optimized nanoemulsion formulation was incorporated into gel and evaluated for in-vitro release, ex-vivo permeation studies, confocal laser scanning microscopy, skin irritation and histopathological studies.Results: The optimized formulation through box-behnken statistical design showed globule size of 20.43 ± 1.50 nm, drug content of 97.05 ± 1.77% and zeta potential of -15.45 ± 0.35 mV. The ex-vivo study confirmed the enhanced delivery of nitrendipine from nanoemulsion gel than compare to drug solution by virtue of better permeation and solubility. Nanoemulsion gel was proved significantly superior by confocal laser scanning microscopy for satisfactory permeation and distribution of gel, deep into the rat skin. The optimized gel was found with no allergic dermal effects and was proved safe by histopathological studies for transdermal application.Conclusions: Results reveals that developed nitrendipine nanoemulsion gel overcomes the limitation of low penetration and accentuate permeation through albino Wistar rat skin. It was concluded that nanoemulsion gel could be utilized as a potential carrier for transdermal delivery of nitrendipine.

Nitrendipine and Dementia: Forgotten Positive Facts?

Nowadays, there are about 50 million people suffering from dementia worldwide. In 2030, it is expected that there will be 82 million people living with dementia and in 2050, their number should reach 152 million. This increase in the number of people with dementia results in significant social and economic problems. Therefore, researchers attempt to reduce risk factors causing the development of dementia such as high blood pressure. Epidemiological studies have shown that hypertension increases the risk of dementia at an older age. It can, therefore, be assumed that hypertension therapy will reduce the risk of dementia. However, previous clinical studies have shown that the efficacy of different antihypertensive drugs differs in this respect. The drug group that appears to be the most effective in these analyses is calcium channel blockers (CCBs). The most significant preventive efficacy in terms of protection against dementia has been demonstrated with nitrendipine. Its use is, therefore, particularly advantageous in elderly patients with systolic hypertension who are at high risk of dementia. The purpose of this study is to restore the discussion on the prevention of vascular dementia and Alzheimer's dementia with nitrendipine in indicated hypertonic patients. The authors performed a literature search of available sources describing the issue of dementia, hypertension and its treatment with nitrendipine. In addition, they made a comparison and evaluation of relevant findings. The results of the detected research studies indicate that nitrendipine is able to reduce the incidence of dementia [Alzheimer's disease (AD), vascular and mixed] by 55%. The treatment of 1,000 patients with nitrendipine for 5 years may prevent 20 cases of dementia. However, what has not yet been explained is the temporal link between hypertension and dementia due to the long-time intervals between hypertension and the development of dementia.

Solubility and Thermodynamic Analysis of Antihypertensive Agent Nitrendipine in Different Pure Solvents at the Temperature Range of 298.15 to 318.15°K.

The aim of the present study was to ascertain the solubility of nitrendipine (NP), an antihypertensive drug in six different pure solvents such as water, ethyl acetate (EA), ethanol, isopropyl alcohol (IPA), polyethylene glycol-400 (PEG-400), and Transcutol at temperature from 298.15 to 318.15 K under atmospheric pressure (p) of 0.1 MPa. Experimental solubility data of NP was fitted with Apelblat and ideal models. The mole fraction solubility of NP was found maximum in PEG-400 (6.85 × 10-2 at 318.15 K) followed by Transcutol (4.65 × 10-2 at 318.15 K), EA (1.68 × 10-2 at 318.15 K), ethanol (2.83 × 10-3 at 318.15 K), IPA (2.69 × 10-3 at 318.15 K), and water (1.29 × 10-7 at 318.15 K). The dissolution activity of NP was observed as an endothermic, spontaneous, and an entropy-driven in most of studied pure solvents. The solubility data of NP obtained in the present study could be useful in purification, recrystallization, and dosage forms design of NP.

Aroma compound diacetyl suppresses glucagon-like peptide-1 production and secretion in STC-1 cells.

Diacetyl is a volatile flavour compound that has a characteristic buttery aroma and is widely used in the flavour industry. The aroma of a food plays an important role in food palatability and thus intake. This study investigates the effect of diacetyl on the satiety hormone, glucagon-like peptide (GLP-1), using the enteroendocrine cell line, STC-1. Diacetyl decreased proglucagon mRNA and total GLP-1 from glucose stimulated STC-1 cells. This dampening effect on GLP-1 appears to be mediated by increasing intracellular cAMP levels, increasing synthesis of the G protein coupled receptor, GPR120, and its recruitment to the cell surface. Voltage gated Ca2+ channels, K+ATP channels and the α-gustducin taste pathway do not appear to be involved. These findings demonstrate that components contributing to food palatability suppress GLP-1. This ability of diacetyl to reduce satiety signals may contribute to overconsumption of some palatable foods.

Comparative Research on the Properties of Nitrendipine Solid Dispersions Prepared by Different Techniques / 中国药学杂志

OBJECTIVE: To compare the properties of nitrendipine/PVP k25 solid dispersions prepared by three different technologies including spray drying, freeze-drying and co-precipitation technology. METHODS: The characteristics of nitrendipine solid dispersions including micromorphology, crystalline profile and intermolecular interactions were analyzed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The dissolution and solubility characteristics were investigated by dissolution apparatus and constant temperature shaker. The crystallization inhibition effect of polymers against the drug in a supersaturated state was investigated by supersaturation crystallization experiment. RESULTS: Nitrendipine existed in an amorphous form in the solid dispersion obtained by spray drying method. Compared with co-precipitation and freeze-drying method, the solid dispersion prepared by spray drying method significantly improved the dissolution and solubility of nitrendipine (P<0.05). The RESULTS: of supersaturation crystallization inhibition test showed that PVP k25 could obviously inhibit the crystallization of nitrendipine in supersaturated state. CONCLUSION: Based on the analysis of the above mentioned properties, nitrendipine solid dispersion prepared by spray drying technology displays the most optimal properties. Spray drying technology is more suitable for the practical production and industrial applications of nitrendipine solid dispersions.

Preparation of starch macrocellular foam for increasing the dissolution rate of poorly water-soluble drugs.

Starch macrocellular foam (SMF), a novel natural bio-matrix material, was prepared by the hard template method in order to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. Nitrendipine (NDP) was chosen as a model drug and was loaded into SMF by the solvent evaporation method. SMF and the loaded SMF samples (NDP-SMF) were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy. In vitro drug release studies showed that SMF significantly increased the dissolution rate of NDP. In vivo studies showed that the NDP-SMF tablets clearly increased the oral bioavailability of NDP in comparison with the reference commercial tablets. All the results obtained demonstrated that SMF was a promising carrier for the oral delivery of poor water-soluble drugs.

Effect of calcium channel blockers on paraoxonase-1 (PON1) activity and oxidative stress.

BACKGROUND: In this study, we investigated the in vitro effects of calcium channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1). METHODS: PON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography. RESULTS: The calcium channel blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors. CONCLUSIONS: Our results showed that calcium channel blockers exhibit inhibitory effects on PON1 at low concentrations. The IC(50) values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K(i) constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.

Impact of genetic polymorphism of SDF1 3A on efficacy of captopril in Chinese patients with essential hypertension / 中南大学学报(医学版)

Objective To explore the association of SDF1 3A genetic polymorphism with susceptibility of essential hypertension and captopril efficacy in patients with essential hypertension.Methods A total of 214 patients with essential hypertension and 228 healthy controls were genotyped for SDF1 3A polymorphism by polymerase chain reaction-restriction fragment length polymorphism assay. Among 39 subjects with different SDF1 3A of genotypes, 13 hypertensive patients simultaneously took oral captopril (25 mg/d) and nitrendipine (30 mg/d), and 12 patients orally received nitrendipine alone for 8 consecutive weeks, and 14 healthy controls did not take any agents. The blood pressure of all subjects was measured to evaluate the therapeutic efficacy. Results There was a significant difference in the plasma SDF-1 level in individuals with AA+AG genotypes or GG genotypes of SDF1 3A treated with nitrendipine plus captopril compared with healthy control (P<0.05). Carriers with AA genotypes of SDF1 3A had lower total protein and globulin than those with GG genotypes (P<0.05). After captopril treatment, hypertensive patients with AA+AG genotypes had bigger attenuated systolic blood pressure compared with those with GG genotypes (P<0.05). Conclusion Genetic polymorphism of SDF1 3A could influence the therapeutic efficacy of captopril in Chinese hypertensive patients.

The cost-effectiveness analysis in patients with primary hypertension by different drug treatment WANG / 中国基层医药

Objective To investigate the economic effects in patients with primary hypertension by four kinds of treatment.Methods 160 cases with primary hypertension were randomly divided into Benazepril group(n=40)、Perindopril group(n=40)、Amlodipine group(n=40) and Nitrendipine group(n=40),and data was evaluated with the pharmacoeconomic cost-effective analysis method.Results Hypertensive efficacy in 4 groups were not sig-nificantly different(x2=3.26,P>0.05);The symptom total score before treatment and after treatment was sisnifi-canfly different(a11 P<0.05);The SF-36 Scale after treatment in 4 groups were higher than before treatment(all P<0.05);The costs of pefindopril was lower than the benazepril.Conclusion Pharmacoeconomies played an important role in optimizing therapeutic scheme,guiding rational drug use and increasing economic effectiveness.

Efficacy and safety of fixed combination of nitrendipine and atenolol in treatment for patients with mild to moderate essential hypertension and their optimal dosage matching / 中华全科医师杂志

Objective To evaluate efficacy and safety of fixed combination of nitrendipine and atenolol in treatment for patients with mild to moderate essential hypertension and their optimal dosage matching.Methods Totally,275 patients with essential hypertension were selcted from seven hospitals in Shanghai,Nanjing and Suzhou,China and randomized into five groups with same proportional probability in a double-blind,double-dummy,parallel active-controlled,multi-center clinical trial,receiving fixed combination of nitrendipine and atenolol at three different dosage matching (nitrendipine/atenolol 5/12.5 mg,5/10 mg,5/7.5 mg for groups 1,2 and 3),and nitrendipine (10 mg for group 4) or atenolol (25 mg for group 5),respectively for eight weeks.Results Mean reduction of diastolic blood pressure (DBP)was (17±7) mm Hg,(18±9) mm Hg and (17±7) mm Hg for groupl,2 and 3,respectively from the baseline,significantly greater than that in groups 4 and 5[(13±7) mm Hg and (12±6) mm Hg,respectively].Mean reduction of systolic blood pressure (SBP) was (21 ±11)mm Hg,(24±12) mm Hg,(23±11) mm Hg,(19±13) mm Hg and (18±9) mm Hg,respectively for the five groups from the baseline,and the reduction in group 2 was significantly greater than that in group 5,with an overall efficacy of 94.4%,98.1% and 88.2% for groups 1,2 and 3,respectively,all statistically higher than that in group 5 (71.4%) with P＜0.01,eight weeks after treatment.The ratio of patients with increased dose of antihypertensive agents in week 5 was lower in group 2 than that in the other four groups,with mild adverse reaction only,no obvious change in laboratory biochemical examinations,and no needs in special management.Conclusions Fixed combination of atenolol and nitrendipine with an optimal doses of 5 mg and 10 mg respepctively was effective and safe for mild and moderate hypertension with good tolerance.