[Comprehensive organoprotection in patients with high cardiovascular risk: the possibility of ramipril from positions of evidence-based medicine].

Ramipril - a drug with a large evidence base. Various aspects of choosing a drug in cardiology from the standpoint of evidence-based medicine are risen from his example.

[Comparative pharmacokinetics of antigrippin-maximum administered in capsules and powder for preparing solutions].

Comparative pharmacokinetics of anti-influenza drug composition Antigrippin-maximum administered in capsules and a powder for preparing solutions has been studied after single administraton in a group of 18 healthy volunteers. Both preparations [manufactured by the Antiviral Research and Production Corporation (St Petersbutg) contain 6 active components, including paracetamol, rimantadine, loratadine, ascorbic acid, calcium gluconate, and rutoside in equal amounts. The concentrations of unchanged paracetamol, rimantadine, and loratadine in the blood plasma were degtermined by HPLC with mass-spectrometric and UV detection. The pharmacokinetic parameters of allindicated active components exhibited no detectable distinctions, except for the time to attaining maximum concentration ofparacetamol and the value of the maximum concentration of loratadine.

[Bioequivalence of anvifen and phenibut].

An open randomized crossover test on 18 healthy volunteers was used to study the pharmacokinetics of anvifen (acting substance, aminophenylbutyric acid) manufactured in capsules at the Joint-Stock Company "Antiviral" (Russia). The test was performed after single peroral administration in comparison with phenibut tablets of the same manufacturer. The concentration of unchanged aminophenylbutiric acid in the blood plasma was measured by HPLC with UV detection. It is established that anvifen and phenibut are bioequivalent in terms of pharmacokinetics.

[Pharmacokinetics of domestic actoprotector drug Metaprot in healthy volunteers].

Pharmacokinetics of the actoprotector Metaprot, an original Russian drug, has been studied in a group of healthy adult volunteers. Metaprot in capsules was administrated orally as a single dose of 250 mg. The concentration of the active substance (ethylthiobenzimidazole) in the blood serum was determined by high-performance liquid chromatography (HPLC) with UV detection. The pharmacokinetic parameters were calculated by the model-independent method. The peak concentration of ethylthiobenzimidazole in plasma was Cmax = 0.91 +/- 1.05 microg/ml and the average time to peak concentration was t(max) = 1.06 +/- 0.16 h. A polymodal character of the distribution of pharmacokinetic parameters in the test group was revealed.

[Determination of cefixime blood plasma levels by HPLC].

For comparative study of the pharmacokinetics of Cemidexor (capsules of 100 mg) and Suprax (capsules of 400 mg), a method of HPLC with quantitative determination of cefixime (the active substance in the drugs) in the blood plasma of patients with UV detection was developed. The data teproducibility with an account of the admissibility criterion was observed within the interval of all the concentrations (0.06-10 mcg/ml). The accuracy and correctness of the method also corresponded to the admissibility criteria. The lower limit of the quantitative determimation of the cefexime blood plasma levels was 0.06 mcg/ml. The pharmacokinetics was studied with the open crossed randomized method. The results were used for calculation of the pharmacokinetic parameters required for estimation of the bioequivalence of the drugs. The statistical analysis of the pharmacokinetic parameters showed that Cemidoxor and Suprax were bioequivalent.

[Comparative study of azithromycin pharmacokinetics in healthy volunteers in open cross randomized procedure]. / Izuchenie sravnitel'noi farmakokinetiki preparatov azitromitsina u zdorovykh dobrovol'tsev otkrytym randomizirovannym perekrestnym metodom.

A method of quantitative determination of azithromycin in HPLC with mass spectrometric detection was developed. The detection limit is 0.5 ng/ml. The method was used in the study of pharmacokinetics and bioequivalence of Zi-Factor (capsules of 250 mg of azithromycin made by Veropharm, Russia) vs. reference-drug. The pharmacokinetic study was performed by the open cross randomized procedure in 18 volunteers. The pharmacokinetic parameters required for estimation of the drug bioequivalence were calculated. The statistical analysis of the pharmacokinetic parameters revealed bioequivalence of Zi-Factor and the reference-drug.

[Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and antiaggregant]. / Aksolong: novaia bukkal'naia forma atsetilsalitsilovoi kisloty dlia primeneniia v kachestve antiagreganta.

AIM: Study of the tolerance and pharmacodynamic and pharmacokinetic characteristics of ascolong, a new buccal dosage form of aspirin containing a very low dose of acetylsalicylic acid (ASA): 12.5 mg. MATERIALS AND METHODS: The study was carried out in 43 healthy men (assessment of the drug tolerance) and 19 male patients with coronary disease or cerebrovascular disorders. In 10 patients the antiaggregant efficacy of ascolong administered once or regularly (for 2 weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of each course before and 2, 4, and 24 h after the drug intake. RESULTS: Ascolong containing a very low dose of ASA exerts a reliable antiaggregant effect after a single and regular intake, although this effect is less manifest than after aspirin tablets. Profiles of ASA concentrations in the blood were studied. Transbuccal entry of ASA in systemic circulation decelerated its metabolism into a less active metabolite, salicylic acid, due to which fact the ASA microdose had an expressed antiaggregant effect. The drug was sufficiently well tolerated. CONCLUSION: The new buccal film form of aspirin containing a very low dose of ASA possesses a good antiaggregant effect and is promising in subjects with contraindications to oral intake of aspirin.

[Chronopharmacokinetics of nadolol in patients with arterial hypertension]. / Khronofarmakokinetika nadolola u bol'nykh arterial'noi gipertenziei.

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.), in daytime (15.00 p.m.) and in the evening (20.00 p.m.). The concentration of nadolol in the blood serum and urine was determined by high performance liquid chromatography with fluorescence detection. Analysis of the obtained data showed maximum blood serum nadolol concentration and the area under the concentration--time curve to be lower (93 ng/ml and 1786 ng h/ml) in the case of evening medication, and the peroral clearance and kinetic distribution volume to be higher (44.8 l/h and 940 l) than after morning medication (188 ng/ml, 2816 ng h/ml, and 28.4 l/h and 650 l, respectively). The corresponding parameters after daytime medication had intermediate values. The half-life period, mean retention time, and time of achievement of maximum blood serum nadolol concentration did not depend on the time of medication and were in the range of 15.2-15.8 h, 21.1-22.0 h, and 2.9-4.0 h, respectively. The pharmacokinetic parameters characterizing nadolol excretion with the urine were independent of the time of its intake. On the basis of the character of the detected circadian changes in the parameters of nadolol pharmacokinetics it is suggested that these changes reflect the circadian variations in the absorption of the drug in the gastrointestinal tract.

[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]. / Farmakokinetika propranolola i ego kon''iugirovannykh metabolitov u bol'nykh khronicheskoi ishemicheskoi bolezn'iu serdtsa i arterial'noi gipertenziei pri odnokratnom i kursovom prieme.

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. Thus the results presented show that potentially active 4HOP-Sulf and S-PG (which undergoes a partial deconjugation in an organism at oral administration) may contribute essentially to the value and duration of the P pharmacological effect.

[The pharmacokinetic interaction of propranolol and nifedipine in patients with angina of effort]. / Izuchenie farmakokineticheskogo vzaimodeistviia propranolola i nifedipina u bol'nykh so stenokardiei napriazheniia.

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 latter occurs at the level of their pharmacodynamic effects.

[The pharmacokinetics of propranolol when used with the propercuten transdermal therapeutic system (experimental data)]. / Farmakokinetika propranolola pri primenenii transdermal'noi terapevticheskoi sistemy properkutena (éksperimental'nye dannye).

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. The rate of drug administration to the systemic bed was 0.08 mg/h per cm propercuten. The constant injection rate was maintained during 5 days, but when propercuten was withdrawn the elimination time of propranolol was 24 hours.

[Differences in hemodynamic effects of the cardioselective beta-adrenoblocker acebutolol and non-selective beta-adrenoblocker propranolol in long-term antihypertensive therapy]. / Osnovnye razlichiia gemodinamicheskikh éffectov kardioselektivnogo beta-adrenoblokatora atsebutolola i neselektivnogo beta-adrenoblokatora propranolola pri dlitelnoi antigipertenzivnoi terapii.

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 antihypertensive effect of acebutolol, 400-800 mg/day, was revealed after 2 weeks of its use and persisted within the entire 12 weeks of therapy. The drug was well tolerated. In contrast to propranolol, a non-selective beta-adrenoblocker having no intrinsic sympathomimetic activity, acebutolol failed to produce adverse effects, such as by decreasing cardiac output and increasing total peripheral vascular resistance. The agent had a less negative chronotropic effect.

[The polymorphism of pachycarpine oxidation]. / Polimorfizm okisleniia pakhikarpina.

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. In 25 patients of the group, the pachycarpine metabolic ratio was evaluated after quinidine, 50 mg. Twenty-two patients with a relatively low metabolic ratio showed a dramatic (several times) increase, while in 3 patients with the prior metabolic ratio higher than 70, the effect of quinidine was insignificant. The findings suggest that pachycarpine oxidation is genetically polymorphic and similar to the polymorphism of sparteine/debrisoquine oxidation. Pachycarpine may be used as a marker in phenotyping the population.