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.

Anticonvulsant activity of nitrendipine in albino mice.

Background: The objective is to evaluate the anticonvulsant activity of nitrendipine in seizure-induced mice. Methods: Albino mice (25-30 g) of either sex were randomly selected and divided into four groups of six mice each. After overnight fasting, Group I received 0.25 ml of propylene glycol and served as the control, Group II received valproic acid (110 mg/kg orally) as standard, Groups III received 5 mg/kg of nitrendipine and 100 mg/kg of valproic acid, Group IV received 5 mg/kg of nitrendipine and 75 mg/kg of valproic acid, and Group V received 5 mg/kg of nitrendipine and 50 mg/kg of valproic acid all of which were administered orally 60 mins prior to the test in this acute study. The anticonvulsant activity was screened using maximal electroshock (MES) model and pentylenetetrazole (PTZ) model. Results: The nitrendipine showed a considerable reduction in the duration of hindlimb extensor phase in MES model and also delayed the latency of seizures induced by PTZ when compared with control group. The probable mechanism of anticonvulsant action of nitrendipine could be due to its interference with the gamma amino butyric acid type aminergic mechanism, modulation of nicotinic, and N-methyl-D-aspartate receptors. Conclusion: Nitrendipine possesses the anticonvulsant activity and has a beneficial role in epilepsy.

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.

Study on Co-grinding Method Improving the Dissolution Rate of Nitrendipine in Vitro / 中国药房

OBJECTIVE: To improve the dissolution rate of nitrendipine in vitro using co-grinding method.METHODS: Single-factor test was adopted to detect effect of phases of co-grinding,category of excipients (MCC,PVPk30,HPC,HPMC),time (0,10,20,30,40,50,60 min) of co-grinding and ratio of principal component to excipients (1 ∶ 1,1 ∶ 2,1 ∶ 3,1 ∶ 4,1 ∶ 5,1 ∶ 6,1 ∶ 7,1 ∶ 8,1 ∶ 9) on in vitro dissolution of nitrendipine power and tablet.RESULTS: The condition of co-grinding method was as follows: dual co-grinding phase,HPC or MCC as excipients,co-grinding time of 40 min,ratio of principal component to excipients was 1 ∶ 4.Accumulative dissolution rate of nitrendipine powder was more than 80% within 10 min and that of nitrendipine tablet was more than 80% within 40 min.CONCLUSION: Co-grinding method can improve the dissolution rate of poorly water-soluble nitrendipine in vitro under suitable condition.

Detection of Nifedipine,Nitrendipine and Nimodipine Added in Chinese Patent Medicine Illegally by LC-MS / 中国药房

OBJECTIVE: To develop a rapid, accurate and sensitive method for the determination of nifedipine, nitrendipine and nimodipine which were added into traditional patent medicine illegally. METHODS: The LC-MS method was used to detect the extractive of Chinese patent medicine for antihypertension in respects of relative molecular mass, tandem mass spectrometry fragment, retention time, UV spectrum. The compounds added into the Chinese patent medicine were identified by comparing with standard sample in terms of spectrum, chromatographic and mass spectrometric behavior. RESULTS: According to four aspects of determination, nifedipine, nitrendipine and nimodipine were found in three kinds of Chinese patent medicine for antihypertension. CONCLUSION: The method is selective and sensitive for the detection of nifedipine, nitrendipine and nimodipine which were added into traditional patent medicine illegally.

Preparation of Nitrendipine Sustained-release Pellets and the Influencing Factors / 中国药房

OBJECTIVE:To investigate the technological factors that influence the drug release of nitrendipine sustained-release pellets.METHODS:The nitrendipine sustained-release pellets were prepared by extrusion-spheronization technology.By means of in vitro drug release test,the factors that influence the drug release including the amount of the wetting agent and the concentration of ethanol,extrusion speed,spheronisation speed and spheronisation time were investigated to optimize the technological conditions.RESULTS:The amount of the wetting agent and the concentration of ethanol had significant effects on drug release.The optimal concentration of ethanol was less than 35% and the optimal amount of the wetting agent was about 44 mL.Extrusion speed,spheronisation speed and spheronisation time had certain effects on drug release,and their optimal values were 48 r?min-1,1 400 r?min-1 and 5 min,respectively.CONCLUSION:The nitrendipine sustained-release pellets prepared in the above-mentioned technological conditions are up to the standard in drug release velocity.

Effect of Atenolol on the Pharmacokinetics of Nitrendipine in Healthy Volunteers / 中国药房

0.05).CONCLUSION:Single oral dose of atenolol had no significant effect on the pharmacokinetics of nitrendipine.

Beneficial effects of nitrendipine on diabetic cardiomyopaty in rats / 中国糖尿病杂志

The effects of nitrendipine (Nit) on myocardial contractility, myocardial succinate de-hydrogenase (SDH) and cytochrome oxidase (CCO) activities in streptozotocin (65mg/kg) diabetic rats were studied. Four weeks after the induction of diabetes, the rats were treated with Nit (30mg ?kg -2/day) for 4 weeks. The results showed that ventricular diastolic function was affected after 4 weeks of diabetes, and both ventricular diastolic and systolic functions were obviously involved after 8 weeks. These changes were significantly improved in diabetic rats receiving Nit treatment. The myocardial SDH and CCO activities in diabetic animals were markedly lower as compared to controls. The attenuation of these enzyme activities in diabetic rats was significantly reversed by administration of Nit. These findings suggest that Nit treatment may exhibit some beneficial effects on diabetic cardiomyopathy.

Effect of Nitrendipine on the Blood Pressure of Mild Hypertensives

Fifty patients with mild essential hypertension were studied to evaluate the efficacy of once-daily regimen of nitrendipine, 10~20mg daily for 12 weeks. 1) Thirty-Seven patients completed the study and showed -9% change in mean arterial headache etc. 2) Eight patients were dropped out because of side reaction, namely flushing, palpitation, headache etc. 3) Ambulatory blood pressure monitoring before and after treatment in 3 patients confirmed the drug efficacy revealing 9% decrement in mean blood pressure and 46% decrease in % elevated BP. 4) Twenty patients who were controlled with other hypotensive drugs were well controlled & maintained the blood pressure in normal range after switching to nitrendpine 10~20mg daily. In conclusion, citrendipine is a safe and good antihypertensive calcium antagonist in the treatment of mild hypertensives with 10~20mg of once-daily dosage.

Eficácia anti-hipertensiva da nitrendipina por 24 horas / Antihypertensive efficacy of nitrendipine for 24 hours

Estudar a eficácia anti-hipertensiva da nitrendipina por 24 horas. Vinte indivíduos com hipertensäo arterial primária leve a moderada. O estudo foi do tipo duplo-cego, com 90 dias de duraçäo. Após 15 dias sem drogas, os pacientes forma divididos aleatoriamente em dois grupos: 1) uso de nitrendipina 20 mg por 30 dias; 2) uso de placebo por 30 dias. Após outros 15 dias de "wash out", os grupos foram cruzados. A pressäo arterial foi avaliada por monitorizaçäo ambulatorial de 24 horas. A pressäo arterial sistólica média das 24 horas, da fase com nitrendipina foi significativamente (p > 0,0001) menor (127,7 ñ 8 mmHg) do que a com placebo (139,2 ñ 8 mmHg) do que a com placebo (139,2 ñ 8 mm Hg); a pressäo arterial diastólica média de 24 horas foi significativamente (p < 0,0001) menor com nitrenpidina (84,6 ñ 4 mmHg) do que com placebo (90,7 ñ 5 mmHg). As demais médias de 24 horas näo diferiram significativamente entre si. A nitrendipina mostrou-se anti-hipertensivo seguro e eficaz durante as 24 horas. A droga reduz as cifras tensionais mantendo o ritmo circadiano da pressäo arterial sem produzir períodos de hipotensäo arterial

Purpose: To evaluate the efficacy of nitrendipine 20 mg OD in mild to moderate hypertensive subjects. Patients and Methods: Twenty patients followed for 90 days. The protocol was a double blind placebo control trial using 24 hours ambulatory blood pressure monitoring system for pressure and heart rate observations. After 15 days without any drug patients were randomly assigned to the study divided into two subgroups: one remained 30 days using placebo and the other nitrendipina. After a new 15 days washout period there was a cross over of the study groups and then other 30 days of follow-up. Results: The 24 hours mean systolic blood pressure decreased (p < 0.0001) with nitrendipine (127.7 ± 8 mmHg) in relation to placebo (139.2 ± 8 mmHg); the mean diastolic blood pressure decreased (p < 0.0001) with nitrendipine (84.6 ± 4 mmHg) in relation to placebo (90.7 ± 5 mmHg). There were no signifcant changes on heart rate and body weight. Conclusion: Nitrendipine seems to be a safe and efficient antibypertensive agent for 24 hours blood pressure control. The drug can decrease blood pressure levels without signifcant changes over the circadian pattern of the 24 hours blood pressure curve and without unwanted drop of blood pressure levels.

Eficácia e tolerabilidade de um novo bloqueador dos canais de cálcio (Nitrendipina) no tratamento da hipertensäo arterial / Efficacy and tolerability of a new calcium antagonist (nitrendipine) in the treatment of hypertension

Objetivo: Avaliar a eficácia e a tolerabilidade da monoterapia por nitrendipina, 20 mg ao dia, em portadores de hipertensão arterial sistêmica leve ou moderada. Material e Métodos: Vinte pacientes submetidos durante seis semanas a estudo aberto comparado (droga x placebo), avaliados através de pressão arterial em posição ortostática, supina e após manobra de hand-grip a cada duas semanas e exames laboratoriais no início e final do estudo. Resultados: As pressões médias sistólica e diastólica apresentaram queda significativa no grupo tratado, nas posições supina (161 mmHg ± 11 para 138 mmHg ± 5 e 105 mmHg ± 5 para 81 mmHg ± 7 -p < 0,05), ortostática (153 mmHg ± 13 para 132 mmHg ± 13 e 104 mmHg ± 5 para 81 mmHg ± 7 -p < 0,05) e após hand-grip (170 mmHg ± 21 para 148 mmHg ± 22 e 108 mmHg ± 5 para 85 mmHg ± 7 -p < 0,05). O grupo placebo não apresentou variações significativas das pressões médias sitólica e diastólica em quaisquer das condições: supina (168 mmHg ± 8 para 168 mmHg 18 e 107 mmHg ± 5 para 107 mmHg ± 3 mmHg), ortostática (167 mmHg ± 9 para 163 mmHg ± 14 e 107 mmHg ± 5 para 107 mmHg ± 4) e após hand-grip (178 mmHg ± 17 para 173 mmHg ± 16 e 107 mmHg ± 4 para 108 mmHg ± 6. Não houve modificação significativa das médias da freqüência cardíaca em ambos os grupos após o tratamento. A elevação da freqüência cardíaca verificada após manobra de hand-grip também não se modificou. Dos eventuais efeitos adversos, observavam-se cefaléia, palpitação e tontura, que estiveram presentes em ambos os grupos (placebo e nitrendipina). Os exames eletrocardiográfico, radiológico e laboratorial não se alteraram ao longo do estudo...

Purpose: Assess the efficacy and tolerability of nitrendipine, 20 mg/day, in mild to moderate essential hypertension (diastolic blood pressure 95 to 114 mmHg). Material e Methods: Twenty patients in an open comparative trial (drug x placebo) during six weeks. Blood pressure and heart rate were measured in ortostatic and supine position and after hand-grip manewre every two weeks. Results: Systolic and diastolic blood pressure fell significatively in the treated group by the end of the study-supine (161 mmHg ± 11 to 138 mmHg ± 13 and 105 ± 5 to 81 mmHg ± 7 p < 0,05) and ortostatic position (153 mmHg ± 13 to 132 mmHg ± 13 and 104 mmHg ± 15 to 81 mmHg ± 7, p < 0,05) and after hand grip maneuver (170 mmHg ± 21 to 148 mmHg ± 22 and 108 mmHg ± 5 to 85 mmHg ± 7 p< 0,051. Significant modifications were not observed in systolic and diastolic blood pressure in placebo group under the following conditions: supine (168 mmHg ± 8 to 168 mmHg ± 17 and 107 mmHg ± 5 to 107 mmHg ± 3) and ortostatic positions (167 mmHg ± 9 to 163 mmHg ± 14 and 107 mmHg ± 5 to 107 mmHg ± 4) and after hand grip maneuore (178 mmHg ± 17 to 173 mmHg ± 16 and 107 mmHg ± 4 to 108 mmHg ± 6). Significant changes in heart rate did not occur in both groups after treatment. Heart rate elevation observed after hand grip maneuvre did not change. Adverse effects like headache, palpitation and dizziness occurred in both groups. Eletrocardiogram, x-ray and blood chemistries were not modified during the trial...

Uinical Observation on Antihypertensive Effects of Nitrendipine

1) Daily dose was 10-20mg Q.D. for 12 weeks. 2) Mean systolic and diastolic pressure were decreased by 49mmHg(25.9%), and 18mmHg(16.8%) respectively. But there was no significant change in heart rate before and after treatment. 3) Systolic and diastolic blood pressure were stably maintained on the whole day. 4) There were no significant side effects except two cases of aggravated congestive heart failure and hypertension. 5) There were no significant changes on hematologic & biochemical parameters before and after treatment.

STUDIES OF HYPOTENSIVE RESPONSE OF NITRENDIPINE, MNIFEDIPINE AND THEIR OIL PREPARATION / 中国药理学通报

The present experiments were designed to compare the antihypert-ensive effects of nitrendipine, m-nifedipine and their oil preparation in conscious renal hypertensive rats The left renal artery was narrowed by a silver clip of 0.2mm diameter under anaesthesia.The systolic blood pressure was measured by the tail cuff method. Nitrendipine and m-nifedipine dissolved in peanut oil ( 20mg/ml ) ; 20mg/kg were given im every other day for 4 weeks.Using sum of squares of deviations from mean in comparison with the untreated control animals the results showed that the 2 drugs reduced the blood pressure significantly (P

Purification and bioactivity of cardiotoxin-13 from venom of naja atra and effects of nitrendipine on its cardiotoxicity / 中国药理学通报

AIM To purify cardiotoxin from Naja atra venom and investigate the relationship between cardiotoxicity of cardiotoxin and coronary artery spasm induced by cardiotoxin. METHODS Cardio toxin 13 (CTX 13) was fractionated and purified by chromatography and gel filtration from Chinese cobra (Naja atra) venom. The cardiotoxicity were observed in rat in situ, its isolated heart preparation and papillary muscle preparations. RESULTS Ion exchange chromatography of lyophilized cobra venom on SP Sephadex C 50 yielded 15 fractions, of thses fractions, cardiotoxic activities were found in fraction 11, 12, 13, and 14. Gel filtration and Ion chromatography of fraction 13 on Sephadex G 50 and SP Sephadex C 25 were performed consecutively and CTX 13 was obtained. It was homogeneous on polyacrylamide gel electrophoresis with MW= 7 769 ku, and 60 amino acid residues. The iv LD 50 in mice was 0 756 mg?kg -1 . CTX 13 increased the coronary resistance and reduced the contractility of rat Langendorff heart preparations. Systolic standstill finally occurred. When the heart preparations were pretreated with nitrendipine, an calcium channel blocker, the resistance seldom increased. The contractility slightly decreased at the beginning and then significantly increased. The tonus of contraction did not occurred. CTX 13 induced dose dependent contraction of pig coronary artery ring segments. Nitrendipine inhibited the action of CTX 13 on the coronary ring segments. However, nitrendipine had no effects on the action of CTX 13 in the rat papillary muscle preparations. The MLD of CTX 13 by venoclysis was changed from (444 7?28 5) ?g?kg -1 to (541 1?23 2) ?g?kg -1 in anaesthetized rats while the rats were pretreated with nitrendipine. CONCLUTION The coronary artery spasm may be one of the causes of death due to CTX 13.