Nanocomplex of Berberine with C Fullerene Is a Potent Suppressor of Lewis Lung Carcinoma Cells Invasion In Vitro and Metastatic Activity In Vivo.

Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber' low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C fullerene (C).

[Chronopharmacokinetics of nadolol in patients with arterial hypertension].

The pharmacokinetics of nadolol in blood serum and its excretion in the urine were studied in 6 male patients (aged from 35 to 59 years) with arterial hypertension for 48 h and, respectively, 72 h after a single per os administration of nadolol in a dose of 80 mg in the morning (9.00 a.m.

Solid-phase extraction on Styrosorb cartridges as a sample pretreatment method in the stereoselective analysis of propranolol in human serum.

Sample pretreatment using solid-phase extraction (SPE) on cartridges filled with small-particle Styrosorb porous polystyrene-based sorbent has been used in the analysis of propranolol enantiomers in human serum by high-performance liquid chromatography (HPLC) with fluorescent detection. SPE on Sep-Pak C18 cartridges was used as a reference pretreatment method. The propranolol content of the samples was determined by achiral normal-phase HPLC and the enantiomeric ratio of propranolol (S/R) was then determined by chiral HPLC on a column with silica-bonded cellulose-tris(3,5-dimethylphenyl carbamate).

[The pharmacokinetics of propranolol and its conjugated metabolites in patients with chronic ischemic heart disease and arterial hypertension with a one-time and course intake of the drug].

Pharmacokinetics of propranolol (P), 4-hydroxy-propranolol sulfate (4HOP-Sulf), and glucoronides of pharmacologically active S-enantiomer P (S-PG) and ballast R-enantiomer of P (R-PG) in the blood serum of 21 patients with chronic ischemic heart disease and/or arterial hypertension has been studied at a single and course oral P administration. The values od AUC and T1/2 for potentially active 4HOP-Sulf were significantly higher than those for unchanged P at a single and course administration. The values od AUC and T1/2 for for S-PG were approximately three times higher than those for P-PG after both a single and course administration.

[The clinical pharmacology of antianginal agents].

This paper provides the basic advances made in studying the clinical pharmacology of antianginal agents (AAs), demonstrates the contribution of current tools for evaluating their antianginal effects, namely pharmacodynamic studies using pair bicycle ergometry and repeated treadmill exercises, 24-hour ECG monitoring, pharmacokinetic studies. It shows that AAs can be chosen on an individual basis. The authors present pharmacodynamic characteristics of a number of new AAs from nitrates (trinitrolong, dinitrosorbilong, etc.

[Proxodolol pharmacokinetics in rats and rabbits].

In non-inbred rats, the pharmacokinetics of proxodolol was studied after its intravenous administration in a dose of 1 mg/kg or oral use in a dose of 50 mg/kg as 1% aqueous solution, in Chinchilla rabbits, it was examined after intravenous administration in a dose of 1 mg/kg as 1% aqueous solution and oral use in a dose of 40-50 mg/kg as 40-mg tablets. The equilibrium dialysis method was applied to explore proxodolol binding to human and rat serum proteins in vitro. Proxodolol was demonstrated to be slightly distributed in the rat peripheral tissues and more actively in the rabbits (the stationary distribution volume was 0.

[The pharmacokinetic interaction of propranolol and nifedipine in patients with angina of effort].

A comprehensive study was undertaken to examine the pharmacokinetic and pharmacodynamic interaction of propranolol and nifedipine in 11 patients with stable angina of effort who were treated for a long time. It was shown that when the agents were given in combination, the patient's plasma generated the same profiles of their concentrations as used alone. This suggests that the propranolol + nifedipine combination is safe from the point of their pharmacokinetic interaction.

[Differences in hemodynamic effects of the cardioselective beta-adrenoblocker acebutolol and non-selective beta-adrenoblocker propranolol in long-term antihypertensive therapy].

The cardioselective beta-adrenoblocker acebutolol used as a course therapy for 12 weeks was found to be a highly beneficial antihypertensive agent. The antihypertensive effect of the agent given in doses of 400-800 mg/day was as pronounced and prolonged as that of propranolol, 80-160 mg/day, though there is a tendency for acebutolol to show its complete or partial antihypertensive effect rather at the end of monotherapy than propranolol. At the same time the bradycardiac effect was more pronounced in propranolol therapy.

[The absence of stereoselectivity in propranolol uptake by the lungs].

Propranolol (P) is known to be actively captured by the lungs of experimental animal and man. To elucidate the mechanism of the phenomenon, the authors studied the P enantiomeric ratio in the serum from the left ventricle 0-10, 10-20 and 20-30 s after bolus injection of P (0.5 mg) into the pulmonary artery of 8 patients catheterized for coronary angiography.

[The polymorphism of pachycarpine oxidation].

The ratio of urinary excretory pachycarpine to its oxidized metabolites, 2- and 5-dehydropachycarpines (metabolic ratio) was determined in a selective group of 81 unrelated cardiac patients from a Moscow Caucasian population given pachycarpine in a dose of 25 g. The metabolic ratio distribution was shown to be bimodal. Ninety five per cent of the patients had the metabolic ratio lower than 28 while 4 (5%) patients higher than 70.

[Various aspects of the anti-aggregatory action of diltiazem and cordaphene in patients with ischemic heart disease].

Some aspects of the antiaggregatory action of calcium antagonists were studied in 50 patients with stable angina pectoris. Dilzem (diltiazem) and cordaphene (nifedipine) were tested for their effects on the erythrocytic component of hemostasis, taking into account their capability of suppressing hemolysis, which made ADP, an important thrombocytic activator, enter the blood flow. The two agents significantly reduce the concentration of plasma ADP, free hemoglobin, diminish mechanical erythrocytic resistance, and block platelet aggregation to a varying degree.

[Comparative effectiveness and biological equivalency of new nifedipine preparations in patients with exercise-induced stenocardia].

The effectiveness of fenigidin and cordafen was studied in comparison with placebo and corinfar after a single administration during pharmacodynamic investigations with tredmill in 14 patients with stable exertional angina. Blood nifedipine concentrations were also compared. The potency of fenigidin was shown to be weaker than that of corinfar.

Development of tolerance to nifedipine in patients with stable angina pectoris.

1. The possibility of development of tolerance to the anti-ischaemic and anti-anginal effects of nifedipine during sustained administration for 2 months was studied in 15 patients with stable angina pectoris by means of repeated exercise tests on a treadmill. 2.

[Relation of the anti-anginal effect and blood serum level of verapamil in patients with exercise-induced stenocardia].

In 9 patients with stable angina pectoris of effort the authors studied the relation between the effect of verapamil in single and regular administration and concentration of invariable preparation and its primary metabolites in the blood serum. Antiischemic effect of verapamil was assessed with use of repeated identical and individual loads on treadmill in combination with ECG monitoring before and at the end of treatment. Linear correlation was established between the effect and concentration of verapamil in the blood serum under the conditions of single and regular administration.

Serum binding of nifedipine and verapamil in patients with ischaemic heart disease on monotherapy.

Serum free fractions of nifedipine, verapamil and some of their metabolites were measured in patients with ischaemic heart disease receiving single oral dose and chronic monotherapy and were compared with those obtained in vitro. The percentages of unbound nifedipine and verapamil in vitro (concentration range 50-200 and 150-400 ng ml-1, respectively) were 2.51 and 7.

[Nifedipine pharmacokinetics in patients with exertion-induced stenocardia after its single and long-term administration].

A study of the causes of tolerance to antianginal effect of nifedipine++, conducted in 12 patients with angina of effort, examined serum pharmacokinetics of nifedipine++ and its primary metabolite (puridine analogue of nifedipine++), after a single 20 or 30 mg dose and at the end of a treatment course (20-40 mg 3-4 times daily for 2 to 6 months). In addition, the effect of nifedipin treatment on nonspecific microsomal hepatic oxidase activity was assessed by means of the antipyrin test. Pharmacokinetics of both unchanged nifedipin and its primary metabolite showed no change through the nifedipin course, suggesting that tolerance to the antianginal effect of nifedipin may be based on altered systemic pharmacologic response rather than altered pharmacokinetics of nifedipin.

[The development of nifedipine tolerance during its regular dosage in patients with stable exertional stenocardia].

The possibility of the development of tolerance to anti-ischemic effects of nifedipine (NF) during chronic administration for 2 months was studied in 15 patients with stable angina pectoris of effort. The duration and degree of the anti-ischemic effect were assessed in terms of similar, individually adjusted exercises performed prior to and repeatedly after NF administration. After acute NF administration the anti-ischemic effect lasting at least 4 h (mean 5.

[Pharmacokinetics of verapamil and its N-dealkylated metabolites in patients with chronic ischemic heart disease undergoing long-term monotherapy].

Pharmacokinetics of verapamil (VP) and its main N-dealkylated metabolites (nor-VP, D-617 and D-620) was studied in 10 patients with chronic ischemic heart disease after administration of the first and last doses of the course of treatment (80-120 mg of VP 3-4 times per day for 4-7 months). The antipyrine test was used in 8 patients simultaneously with the study of pharmacokinetics of VP and its metabolites. At the end of the course a decrease of oral clearance of VP as compared with its beginning (from 3.

[Comparison of the verapamil concentration of human blood serum and saliva].

Verapamil concentrations were measured in the samples of blood serum and saliva taken at the same time in patients with angina of effort within 0.5-24 hr after administration of a single dose of the drug (14 persons) or the last dose of the course (10 persons). A mean ratio of saliva verapamil concentration to blood serum concentration was 0.