[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.

[The relationship between the isosorbide-5-mononitrate concentration and its antianginal effect following the administration of regular and prolonged-action drug forms in patients with stenocardia of effort]. / Sviaz' mezhdu kontsentratsiei izosorbid-5-mononitrata i antianginal'nym éffektom posle priema obychnoi i prolongirovannoi lekarstvennykh form u bol'nykh stenokardiei napriazheniia.

Isosorbide-5-mononitrate (IMN) concentration-antianginal effect relationships were studied in 14 coronary heart diseases patients with stable exertion-induced angina after administration of Efox (Schwarz-Pharma) as two dosage forms: routinely acting tablets (20 mg) and long-acting capsules (50 mg). The antianginal effect index was an increase of treadmill exercise duration (sec) as compared with placebo, the concentration and effect were measured in points 0, 1, 3, and 7 hours after administration, in some patients, investigations were conducted 12 and 24 hours. The two formulations were found to be highly effective drugs whose action lasted 7 hours, by that time the effect of the tablets substantially decreased, which was associated with decreases in drug concentrations. The efficiency of the capsules at this point was significantly higher than that of the tablets. The use of the capsules resulted in tachyphylaxis--rapid decreasing responses to IMN. Following 7 hours of their administration there is a significant decrease in their effect with an increase in IMN concentrations.

[The clinical pharmacology of antianginal agents]. / Klinicheskaia farmakologiia antianginal'nykh sredstv.

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.), calcium antagonists, beta-adrenoblockers (proxodolol, etc.). They have developed a method for assessing the biological equivalence of AAs. The paper discusses the tolerance that can be developed to nitrates and how it can be prevented. It first demonstrates that nifedipine tolerance can develop and that the withdrawal syndrome can occur if nitrates and calcium antagonists are discontinued. There are screening data on various combinations of AAs. A two-stage scheme for choosing an AA therapy is given.

[Sublingual nitroglycerin: the pharmacokinetic changes following long-term treatment with trinitrolong and nitroderm-TTS]. / Sublingval'nyi nitroglitserin: izmenenie farmakokinetiki posle dlitel'nogo lecheniia trinitrolongom i nitrodermom-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. The observed slowing of elimination is probably the cause of the development of tolerance to NH at the long-term treatment, since according to the modern notions the degree of the effect is determined by the rate of NG metabolism.

[New drug forms of isosorbide dinitrate: the problem of an objective evaluation in patients with ischemic heart disease]. / Novye lekarstvennye formy izosorbida dinitrata: problema ob''ektivnoi otsenki u bol'nykh ishemicheskoi bolezn'iu serdtsa.

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. Isodinite had a more pronounced effect than nitrosorbide, although the duration of isodinite effect was shorter than that of nitrosorbide. Plasma ID and its metabolite, isosorbide-5-mononitrate concentrations mirrored exercise duration changes. ID content in the tablets of all formulations studied corresponded to those indicated by the manufacturer. The differences in the efficacy of ID formulations can be attributed to the differences in their bioavailability. Thus, the method used permitted to reveal significant distinctions in the efficacy of different ID formulations. These distinctions must be taken into account in clinical practice.

[A new antianginal preparation: isosorbide-5-mononitrate]. / Novyi antianginal'nyi preparat izosorbid-5-mononitrat.

Repeated treadmill exercise tests were used in 20 patients with stable exercise-induced angina in order to comparatively examine various dosage forms of isosorbide-5-mononitrate (IMN) and isosorbide dinitrate (ID) during their single administration. The antianginal effect of conventional IMN tablets (Monisid, Bulgaria) lasted about 5 hours and 1-2 hours longer than that shown by long-acting tablets (Olicard, FRG) and lasted on an average of 12 hours. There was a correlation between the antianginal effect of IMN and its blood concentration. A significant individual variability was observed in the potency of all the dosage forms of IMN and ID under study. The dosage form of IMN had antianginal effects that were similar and even superior to those exhibited by ID.

[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]. / Analiz sviazi kontsentratsiia--éffekt trinitrata glitserina u bol'nykhstenokardiei napriazheniia posle odnokratnogo primeneniia v lekarstvennykh formakh s prolongirovannym vysvobozhdeniem.

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 0.5-0.6 ng/ml.

[Relation of the anti-anginal effect of nitroglycerin and its blood level in patients with stable exertion-induced stenocardia]. / Zavisimost' antianginal'nogo effekta nitroglitserina ot kontsentratsii ego v krovi u bol'nykh so stabil'noi stenokardiei napriazheniia.

In 8 patients with coronary heart disease and stable angina pectoris of effort, a relationship was examined between nitroglycerin antianginal effects and blood concentration when it was topically applied to the gum (trinitrolong, TNL) and to the skin (nitroderm, ND). A close correlation was found between the antianginal effects and blood concentration (r = 0.97 for TNL and r = 0.81 for ND). The individual correlation coefficients were 0.61 to 0.84 for TNL and 0.31 to 0.79 for ND). In all cases but one, the antianginal effect was demonstrable when blood NG concentration reached 0.75 ng/ml, while in some cases (23%) at a concentration of 0.5 ng/ml or less.

[Pharmacokinetics of glycerin trinitrate (nitroglycerin) after sublingual administration in patients with chronic ischemic heart disease]. / Farmakokinetika glitserina trinitrata (nitroglitsein) posle sublingval'nogo priema u bol'nykh khronicheskoi ishemicheskoi bolezn'iu serdtsa.

Pharmacokinetics of nitroglycerin was studied in 22 patients with ischemic heart disease associated with angina of effort after sublingual intake of 0.5 mg standard granules. The maximal blood plasma concentration of the drug was shown to occur on the average in 4.4 minutes and was 2.56 ng/ml. The half-life in plasma was on the average 6.0 minutes, apparent clearance was 21.9 l/min. The mean retention time of nitroglycerin was 9.5 minutes. Significant fluctuations of pharmacokinetic parameters during repeated examinations in the same patient as well as between the patients were revealed. A sharp asymmetry of distribution of these parameters was observed that makes it necessary to use the mean arithmetical for characterization of the pharmacokinetic parameters.

New transdermal and transmucosal nitroglycerin delivery systems in patients with ischaemic heart disease.

The efficacy of a transdermal (Nitroderm-TTS) and a transmucosal (Trinitrolong) nitroglycerin (NG) formulation has been compared with sublingual NG in 9 patients with ischaemic heart disease and stable angina pectoris. The duration and the degree of anti-ischaemic effect were assessed in terms of similar, individually adjusted work loads performed prior to and repeatedly after drug application in comparison with placebo. The anti-ischaemic effect of nitroderm appeared in 0.5-3 h after administration, reached a maximum in about 3.8 h and persisted for 7.9 h. The maximal nitroderm effect was significantly lower than that of sublingual NG or Trinitrolong. The effect of Trinitrolong was less variable and lasted for 4.6 h. It was evident in all patients 0.5 h after drug administration. Plasma NG levels were monitored in 9 patients after sublingual NG and trinitrolong and in 4 following Nitroderm. The relative bioavailability of Nitroderm and Trinitrolong according to the pharmacokinetic data was 29% and 256%, respectively, of sublingual NG tablets. A therapeutic NG level in blood (0.5 ng/ml) after Trinitrolong appeared much earlier (2 min) than after Nitroderm (1 h). A significant reduction in the effect of sublingual NG was observed during Nitroderm application. Thus, the transdermal NG formulation did not exhibit an antianginal effect lasting for 24 h; transmucosal NG had a relatively short, but more pronounced and stable antianginal effect.

[Dinitrosorbilong--a new Soviet anti-angina preparation. Its comparative pharmacodynamic, pharmacokinetic and clinical study]. / Dinitrosorbilong--novyi otechestvennyi antianginal'nyi preparat. Sravnitel'noe farmakodinamicheskoe, farmakokineticheskoe i klinicheskoe izuchenie.

The efficacy of dinitrosorbilong (DNL)--a new long-acting isosorbid dinitrate (IDN) preparation applied to the gum--was evaluated in 72 coronary patients with stable angina of effort. Repeated treadmill tests revealed antianginal effect of DNL exceeding 8 hours. The degree and duration of DNL action significantly surpassed those of conventional oral IDN tablets and of some other long-acting IDN preparations. The results of pharmacokinetic studies show that DNL bioavailability is 491 +/- 240% as compared to conventional oral IDN tablets. Regular 7-day DNL administration resulted in a significant decrease in the frequency of anginal attacks and in the daily consumption of nitroglycerin tablets as compared not only to the control period but also to the period of conventional IDN tablet therapy.