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Biomedical subjects

C Farsang

Publications and source records attributed to C Farsang.

At least 19 recordsLinked to original sources

Human bioequivalence study of a new nifedipine containing retard filmtablet after single and repeated administration.

A clinical pharmacokinetic bioequivalence study with two retard filmtablet preparations, both containing 20 mg of nifedipine (CAS 219829-25-4) was carried out. The investigated test preparation was Cordaflex 20 mg retard filmtablet. The pharmacokinetic parameters were determined after single and repeated administration in 15 and 16 healthy male volunteers, respectively, in open, randomised studies of cross-over design. Plasma levels of nifedipine were determined by HPLC with electrochemical detection using a robotic sample preparation technique. Statistical comparison of the pharmacokinetic parameters (AUC0-infinity, AUCss, tau tmax, Cmax, Css,min, Css,av, MRT, etc.) calculated from plasma concentration-time curves by ANOVAlog, confidence interval, Schuirman's, Westlake's, Anderson's and Wilcoxon's tests, furthermore the comparison of the clinical results did not show any significant difference between the two preparations. It is concluded that the two preparations are bioequivalent after repeated administration.

Adult

[Captopril treatment of hypertension].

After the brief description of the most important hypertensive pathophysiological processes (renin, angiotensins) which are closely related to angiotensin converting enzyme (ACE) inhibitors as well as to the mechanisms of action of captopril, author summarizes the essential clinical findings from the international and Hungarian literature. A short guideline for the administration of captopril to hypertensive patients is also given.

Antihypertensive Agents

[Effect of fluvastatin on serum lipid levels in essential hypertension].

The efficacy and safety of the HMG-CoA reductase fluvastatin was investigated in a multicenter, open label clinical therapeutic trial in the treatment of hypercholesterinaemia in hypertensive patients (WHO I-II.). 49 patients were involved, 6 patients were dropped out because of th lack of compliance, 43 patients were investigated (mean age: 57.6 +/- 9.4 years, mean blood pressure: 146 +/- 16/88+/- g mmHg (systolic/diastolic). The antihypertensive treatment was unchanged during the study. An 8 weeks low-lipid diet was started if the fasting total cholesterol (TC) level was equal or higher than 6.5 mM/L and the triglyceride level was lower than 4.6 mM/L. After the dietary period fluvastatin treatment was started (20 mg o.d.), if the level of LDL-C was higher than 4,1 mM/L. Blood pressure, heart rate, TC, HDL-C (HDL2-C, HDL3-C), apoA1, apoB, TG were measured at the 4th, 8th, 12th weeks of treatment. LDL-C was calculated with Fridewald equation. The daily dose of fluvastatin was increased to 40 mg, if LDL-C level was higher than 3.5 mM/L after 4 weeks of treatment. 36 patients completed the study (Group B). 7 patients were dropped out at the end of the dietary period, because of the significant decrease of TC and LDL-C levels (Group A). In Group B fluvastatin significantly reduced the level of TC (from 7.22 +/- 0.88 to 5.99 +/- 0.98 mM/L), of LDL-C (from 5.13 +/- 0.71 to 3.95 +/- 0.88 mM/L), and the level of ApoB (from 0.97 +/- 0.26 to 0.85 +/- 0.15 mM/L), but did not influence significantly the level of HDL-C, ApoA1 and TG. The diastolic blood pressure decreased significantly during the dietary period, while after beginning the fluvastatin treatment the decrease of the systolic blood pressure became significant. There was no change in the heart rate. Only minor side effects were observed in 3 patients (dysuria, constipation, lack of appetite). Fluvastatin proved to be an effective and well-tolerated drug in the treatment of hypercholesterinaemia in hypertensive patients.

Aged

[Comparative human pharmacokinetic studies of 20 mg nifedipine-containing Cordaflex and Adalat film coated retared tablets].

Comparative pharmacokinetic studies have been carried out with two 20 mg nifedipine active substance-containing retard film coated tablets, Cordaflex produced by EGIS Pharmaceuticals Co., Ltd. and Adalat of Bayer AG. The pharmacokinetic parameters and the relative bioavailability were determined in 15 and 16 healthy male volunteers, respectively after single and repeated administration in open, randomized cross over study. The plasma concentration of nifedipine was determined by HPLC-ED method, using laboratory robot for automated sample preparation. On the basis of graphical and statistical comparison of the pharmacokinetic parameters (AUC0-infinity, AUCss,0-tau, tmax, Cmax, Css,min, Css,av, MRT, etc.) calculated from the time-plasma concentration curve, moreover on the basis of clinical results, there was no significant difference between the two preparations. In conclusion, the relative bioavailability of Cordaflex and Adalat 20 mg retard tablets did not show significant difference after single and repeated administration.

Administration, Oral

Hungarian Isradipine Study (HIS): long-term (3-year) effects on blood pressure and plasma lipids.

These are the preliminary data of an open multicenter trial of antihypertensive treatment with isradipine as monotherapy (dose, 4.55 +/- 0.56 mg twice daily; n = 11) or isradipine (7.5 +/- 0.63 mg twice daily) in combination with bopindolol (1.16 +/- 0.12 mg once daily; n = 30) administered for 3 years to patients with essential hypertension (WHO classification I or II). Blood pressure was significantly decreased in both treatment groups and there was no indication of resistance to therapy. Plasma levels of total cholesterol and triglycerides were decreased by the end of the second year of treatment, and there was a tendency toward increase in plasma levels of high-density lipoprotein cholesterol (HDL2 or HDL3). The atherogenic index (ratio between total cholesterol and HDL2 plus HDL3) was also decreased. Blood glucose levels remained unchanged in both normoglycemic patients and those with non-insulin-dependent diabetes mellitus (NIDDM) during 3 years of therapy. It is concluded that isradipine is safe and effective when administered long-term in the treatment of hypertensive patients with either hyperlipidemia or NIDDM.

Adolescent

Antihypertensive effect of the calcium antagonist isradipine and lipid profile.

The hypothesis that plasma lipids may modulate the antihypertensive effect of the calcium antagonist isradipine was tested in 85 patients who had essential hypertension. Significant linear correlations were found between the antihypertensive effect of isradipine and plasma levels of total cholesterol and high-density lipoprotein (HDL2 or HDL3) in normotriglyceridemic (n = 63), but not in hypertriglyceridemic (n = 22), patients. From this, we conclude that normal levels of plasma lipids may modulate the function of calcium channels and their interaction with calcium antagonists.

Adult

[The "white coat effect" in hypertensive patients].

The "white coat effect" has been investigated by non-invasive automatic blood pressure monitoring in patients with hypertension, defined by casual blood pressure readings. A significant "white coat effect" has been demonstrated in 30 (32%) of the 93 patients: the average values were 17/9 mmHg and 6 beat/min, the highest values were 37/29 mmHg and 13 beat/min. The examination has been repeated after 24 hours in 11 cases and the phenomenon was reproducible. The "white coat effect" did not disappear even when the changes were compared to the averages of three subsequent automatic blood pressure measurements. There were significantly more women, than men among the "white coat" positive patients. However, no difference was found in age, occupation and the known duration of hypertension. Neither was any correlation between the "white coat effect" and the blood pressure reaction to mental arithmetic test. It is emphasized that the casual readings can significantly overestimate the blood pressure. This finding must be considered especially in the diagnosis of borderline hypertension.

Blood Pressure Determination

Adrenergic and dopaminergic regulation of circulating beta-endorphin-like immunoreactivity in hypertension.

The central alpha-2-adrenergic receptor agonist, clonidine (300 micrograms daily) significantly increased the plasma beta-endorphin-like immunoreactivity (beta ELI) in 12 patients with mild to moderate essential hypertension in a randomized, crossover study. A significant linear correlation between the increase in plasma beta ELI and the decrease in blood pressure (both systolic and diastolic) was found after clonidine administration. The role of the reduced central sympathetic tone, induced by alpha-2-adrenoceptor stimulation, in the elevation of circulating beta ELI can be suggested. The plasma beta ELI increased also significantly after the dopaminergic D-2 receptor agonist, bromocryptine treatment, (5 mg, daily) in 13 patients with borderline and mild essential hypertension in a randomized, crossover study. A significant drop in circulating noradrenaline and in arterial blood pressure and a significant linear correlation between the changes of plasma noradrenaline level and blood pressure was found after bromocryptine administration. There was no correlation between the rise in plasma beta ELI and the decrease in blood pressure after bromocryptine. The importance of the central sympathetic activity and not only a direct pituitary dopaminergic agonist effect on the beta-endorphin secretion can be stressed in the effect of bromocryptine on the immunoreactive beta-endorphin level.

Adult

[The anti-lipidemic effect of Minipress].

Prazosin (Minipress) monotherapy was given to 152 patients with essential hypertension for one year in a multi-center study involving 13 hospitals and university clinics. In three centers serum levels of total cholesterol, HDL-cholesterol and triglycerides were also determined in 32 patients with hypertension and hyper/dys-lipoproteinemia. As a consequence of Minipress monotherapy significant decreases were found in serum level of cholesterol (after three months and also after one year), triglycerides (after one year), while the serum concentration of HDL-cholesterol increased. Atherogenic index (a ratio of total cholesterol over HDL-cholesterol) was significantly decreased by Minipress. As new data showing a causative correlation between hypertension and hyperlipoproteinemia were published in the literature authors, on the basis of their results, suggest to determine lipid profile in every patient with hypertension. They regard Minipress as the first line drug in young patients with "familial dyslipidemic hypertension". When choosing an antihypertensive drug metabolic side effects should be taken into consideration.

Coronary Disease

[Blood pressure lowering effect of nifedipine in smokers and non-smokers].

The authors summarized the relationships between the cardiovascular diseases and smoking. In their retrospective study they studied the acute antihypertensive effect of nifedipine in patients with essential hypertension who were smokers and nonsmokers. They suggest that the antihypertensive effect of nifedipine did not decrease in smokers. Therefore the nifedipine can be the first choice in the antihypertensive therapy in smokers with essential hypertension.

Antihypertensive Agents

Antihypertensive effect of bopindolol: a multi-centre study.

The objective of the study was to investigate the efficacy of different dose levels of bopindolol monotherapy in hypertension. This potent nonselective beta-adrenergic receptor blocker has intrinsic sympathomimetic activity and long duration of action. Forty-four patients with essential hypertension of mild (n = 40) or moderate (n = 4) severity (90 less than DBP less than or equal to 115 mmHg at the end of the placebo period) entered and completed the single-blind, placebo-controlled trial. The study lasted 14 weeks: 2 weeks on placebo, and 12 weeks on active treatment during which the initial dose of bopindolol, 1 mg daily, was augmented up to 1.5 mg, then to 2 mg at four-week intervals until BP normalized or a maximum dose of 2 mg/day bopindolol was reached. The bopindolol was administered once a day in the morning. Patients were seen every other week in the morning before drug taking, when BP and heart rate, supine and standing, a twelve lead ECG and side-effects were recorded. Compared with placebo, supine BP was significantly reduced by bopindolol: from 169 +/- 2/103 +/- 1 mmHg to 148 +/- 3/92 +/- 1, 144 +/- 3/90 +/- 1 and 136 +/- 2/85 +/- 0.6 mmHg at the end of 4, 8 and 12 weeks of treatments, respectively (P less than 0.01 for each). BP changes during standing were similar. Bopindolol lowered the supine heart rate from 84 +/- 2 to 75 +/- 1, 74 +/- 1, 72 +/- 1 beats/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Diagnostic and therapeutic significance of automatic circadian monitoring in hypertension].

A noninvasive, fully automatic blood pressure monitoring system has been developed to make the measurement of blood pressure more reliable and to help individualizing anti-hypertensive therapy. The authors draw attention to the importance of the circadian blood pressure variability and the "white coat hypertension" phenomenon. The error due to overlooking the changes in circadian blood pressure and to the "white coat" effect could be avoided with automatic blood pressure monitoring. Their system consists of two subunits: the Nippon Colin (BP 203 MII) blood pressure monitor, which has been fitted to the Commodore 64 computer by their own interface and data transfer program. Data analyzing and graphic displaying programs have also been developed by them. The diagnostic and therapeutic importance of blood pressure monitoring are demonstrated with representative cases of patients with essential, renoparenchymal and renovascular hypertension. The perspectives of this method in clinical pharmacology are also illustrated and discussed.

Automation

Nifedipine-prazosin interaction in patients with essential hypertension.

In an acute, double-blind, crossover study on 12 patients with essential hypertension, the interaction between nifedipine and prazosin was investigated in the supine position. The effectiveness of the combination of the two active drugs was greater than the combination of either of the drugs plus placebo. The effect of nifedipine was not modified by prazosin pretreatment; however, the effect of prazosin was partly inhibited, i.e., delayed, by nifedipine pretreatment. Therefore, giving prazosin as a first drug and nifedipine as the second drug seems to be a better approach than the reverse.

Adult

Retrospective analysis of clinical data of normotensive and hypertensive pregnant women and their newborns.

The medical history of 256 hypertensive and 263 normotensive pregnant women was analysed retrospectively. There was a negative correlation (P less than 0.01) between the maximal pretreatment diastolic blood pressure and the birth weight of newborns in the hypertensive group. The prevalence of a hypertensive family history, pyelonephritis, proteinuria, delivery by Caesarean section, fetal asphyxia during delivery and death of the newborn during delivery was significantly higher in the hypertensive group than in the normotensive one. The gestational age at delivery was shorter and the birth weight of the newborn was lower in the hypertensive women than in the normotensive women.

Antihypertensive Agents

Dopaminergic-opioidergic interaction is reflected by changes in pituitary hormone secretion in patients with essential hypertension.

In a randomized, double-blind crossover study 13 untreated patients with mild essential hypertension were exposed to submaximal bicycle exercise. Sixty minutes before ergometry 10 mg metoclopramide or placebo, and 10 min before exercise 0.4 mg naloxone or placebo, were given intravenously. Plasma adrenocorticotrophic hormone, beta-endorphin and cortisol levels increased significantly after ergometry, whether performed after placebo, naloxone, metoclopramide or metoclopramide + naloxone treatment. However, only naloxone administration potentiated plasma adrenocorticotrophic hormone, beta-endorphin and cortisol responses to workload. Plasma levels of adrenocorticotrophic hormone, beta-endorphin and cortisol were 45 +/- 14 pg/ml, 6.2 +/- 1.2 pmol/l and 141 +/- ng/ml, respectively, after ergometry, when performed after placebo, but these values were increased to 61 +/- 10 pg/ml, 11.4 +/- 2.8 pmol/l and 207 +/- 22 ng/ml, respectively, after naloxone treatment. This naloxone-induced potentiation of hormonal release was blocked by metoclopramide pretreatment, suggesting a close interaction between dopaminergic and opioidergic mechanisms, regulating hormonal responses to physical exercise.

Dopamine

Clinical studies with captopril treatment of hypertensive patients.

Haemodynamic and humoral effects of captopril were studied in patients with essential and renovascular hypertension. Captopril decreased significantly both systolic and diastolic blood pressure and moderately, it reduced also the heart rate. On the basis of the haemodynamic effects our patients could be divided into two groups: in patients where the total peripheral resistance (TPR) exceeded 2000 dyn x sec x cm-5 during rest, captopril exerted its hypotensive effect by decreasing TPR. In patients in whom TPR was lower, the hypotensive action could be attributed to the reduction of cardiac output (CO). Captopril increased plasma renin activity, and decreased the activity of angiotensin converting enzyme (ACE) in the plasma. In acute study captopril did not influence plasma noradrenaline level but increased it during long-term administration. It did not affect dopamine or adrenaline levels. Captopril had no effect on plasma beta-endorphin concentration, moreover, the opiate antagonist, naloxone, failed to antagonize its antihypertensive effect. Comparing the acute effects of Capoten (Squibb, USA) and Tensiomin (EGIS, HUNGARY) no significant differences were found.

Biomechanical Phenomena

Important clinicopharmacological aspects of captopril.

With a brief description of the physiological role of the renin-angiotensin-aldosterone system in the regulation of blood pressure the most important clinicopharmacological aspects of the converting enzyme inhibitor, captopril, is outlined. Hemodynamic and humoral effects, pharmacokinetics, indications, contraindications, dosage, side effects, drug interactions and usage in diagnostic procedures of captopril is described. The possibility of captopril therapy in children is also discussed.

Asthma

A comparative study of the acute antihypertensive effect of Adalat capsules and Corinfar dragées, two different nifedipine preparations.

The calcium entry blocker nifedipine produces systemic vasodilation and decreases the elevated vascular resistance in hypertensive patients. The authors investigated the acute antihypertensive effect of sublingually administered nifedipine in two different formulas: Adalat capsules and Corinfar dragées. There was no significant difference between both these formulas regarding their effects on blood pressure and heart rate, and their side effects were also similar. The authors conclude that the acute antihypertensive effect of nifedipine, either in capsules or in dragées, is equipotent in essential hypertension.

Administration, Oral