[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.

[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 prediction of enantiomeric differences in the pharmacokinetic parameters of drugs by using a physiological perfusion model].

A physiological perfusion pharmacokinetic model was used to assess the possible differences in the model-independent pharmacokinetic parameters of drug enantiomers (total clearance, mean retention time, half-life and stationary distribution volume), depending on differences in their blood binding and in the values of intrinsic hepatic clearance. The distribution in the organs and tissues and renal clearance of enantiomers were assumed to be equal. The maximally possible values of the relationships of the above parameters were found for enantiomers.

[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.

[The pharmacokinetics of propranolol when used with the propercuten transdermal therapeutic system (experimental data)].

The pharmacokinetic studies of propranolol following the application of the propercuten transdermal therapeutic system were performed in conscious rabbits previously assigned to 3 groups. Different forms of propercuten (forte and mite) were used in different groups, different areas of its application being employed. Pulsed intravenous injections of propranolol were given to Group 1 rabbits to conduct another series of pharmacokinetic studies.

[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 pharmacokinetics and pharmacodynamics of the prolonged-action beta-adrenoblocker nadolol at rest after a single administration to hypertension patients].

The pharmacokinetics and pharmacodynamics of nadolol given in a single dose of 80 mg to 17 patients with mild hypertension were studied by echocardiography at rest. The major pharmacokinetic parameters for nadolol did not differ greatly from those reported in the literature and obtained from volunteers. No correlation was found between endogenous creatine clearance and renal nadolol clearance.

[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.

[The pharmacokinetics of the prolonged-action beta-adrenoblocker nadolol in hypertension patients after a single administration].

The pharmacokinetics of the beta-adrenoceptor blocker nadolol was studied in 30 patients suffering from mild hypertension given a single 80 mg dose of the drug. It has been shown that distribution of the pharmacokinetic parameters in this sample can be assumed normal. Their averages are similar to the reported data on healthy subjects.

[Assessment of rate constants for isolating a metabolite by a model-independent method].

A model-independent method for estimating an elimination rate constant of a metabolite of exogenous substance is suggested as an alternative to known methods. The new method (named the initial slope method) uses blood (plasma) concentration-time data of both the substance and the metabolite obtained after an extravascular impulse input of the substance. The metabolite input is not needed substantially facilitating the experiment.

[The subject of pharmacokinetics and its methodological problems].

Recently the article by V. A. Gor'kov and Iu.

[Sublingual nitroglycerin: the pharmacokinetic changes following long-term treatment with trinitrolong and nitroderm-TTS].

The effect of the long-term use of prolonged medicinal forms containing nitroglycerin (NG)--trinitrolong and nitroderm-TTS on the pharmacokinetics of sublingual NG was studied. A significant change of the pharmacokinetic parameters at the sublingual use of NG both after the long-term treatment with trinitrolong and after therapy with nitroderm was observed: in both cases the time of half-release of NG from plasma and the average time of retention increased, the area under the curve of concentration-time significantly increased and the drug clearance decreased (for trinitrolong the difference in the clearance parameter is significant). While combining the data on both drugs the difference in the last two parameters also becomes significant.

An initial slope method for model structure: independent estimation of the elimination rate constant of a metabolite.

A model structure-independent method for calculating the true elimination rate constant of a primary metabolite is presented. It does not require direct metabolite administration and uses data on drug and metabolite blood (plasma) concentrations after a bolus drug input. The method has been tested and compared with the moment method and the area function method using errorless and errant data simulated on the basis of one- and two-compartment models of the metabolite kinetics.

[New drug forms of isosorbide dinitrate: the problem of an objective evaluation in patients with ischemic heart disease].

In 7 patients with ischemic heart disease and stable angina pectoris the efficacy of three oral isosorbide dinitrate (ID) formulations, nitrosorbide, isodinite and isodinite-retard, was compared. The antianginal and anti-ischemic effects were assessed in terms of exercise treadmill tests performed prior to and repeatedly after (2, 5 and 7 hours) single-dose administration (in comparison with placebo). The efficacy of isodinite-retard only slightly differed from that of placebo.

[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.

[Possibilities of mathematical models of pharmacokinetics].

Mathematical modelling is currently the most rapidly developing branch of pharmacokinetics. Along with such traditional pharmacokinetic aspects as drug absorption, distribution, metabolism, and elimination, the pharmacodynamic area is also becoming actively involved in mathematical modelling. Complex pharmacokinetic-dynamic models are becoming a tool that finds wider application in drug therapy optimization.

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.

[An analysis of the concentration-effect relation of glyceryl trinitrate in patients with stenocardia of effort after its single use in prolonged-release drug forms].

There is a correlation between the plasma concentrations of glycerol trinitrate and the antianginal effects of trinitrolong (application on the gingival mucosa) and nitroderm-TTS (application on the skin) in patients with angina pectoris by Hill's formula. The lower limit on the gingival mucosa) and nitroderm-TTS is 0.5-0.