[Peculiarities and clinical significance of drug pharmacokinetics and pharmacodynamics during pregnancy].

There are relatively few data reported on specific features of drug pharmacokinetics (PK) and pharmacodynamics in pregnancy compared to the non-pregnant state. Changes in maternal physiology and metabolic processes during pregnancy effect on PK and show that standard adult dosing is likely to be incorrect during pregnancy. Physiology-based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women and to correctly predict drug exposure and response on the personal level.

[Gender related characteristics of clinical status and pharmacotherapy of patients with paroxysmal and persistent atrial fibrillation].

Aim of the study was to elucidate gender related characteristics of clinical status and treatment of patients with atrial fibrillation (AF) hospitalized in a department of urgent cardiology of multiprofile clinical hospital. In a retrospective pharmacoepidemiological study we analyzed case histories of 114 men and 79 women hospitalized because of detected and electrocardiografically confirmed paroxysmal or persistent AF. Compared to men women were significantly older, among them there were significantly more individuals older than 75 years (<0.05), and AF developed in women at older age (<0.05). However duration of arrhythmic anamnesis was similar in women and men. Among women we noted greater prevalence of ischemic heart disease; they had higher risk of thromboembolic complications and higher rate of these complications in anamnesis. Rates of obesity and diabetes mellitus were also higher among women. Men more often had isolated arterial hypertension and lung diseases. There were more smokers among men. Women significantly less often received adequate antithrombotic therapy; they were less often subjected to electrical cardioversion. Rate control strategy was more often selected for women.

[The effect of phenobarbital and cimetidine on the elimination kinetics and distribution in the heart and liver of propranolol in rats with acute and chronic inflammations]. / Vliianie fenobarbitala i tsimetidina na kinetiku éliminatsii i raspredelenie v serdtse i pecheni propranolola u krys s ostrym i khronicheskim vospaleniem.

Intravenous administration of propranolol (10 mg/kg) to rats with turpentine-induced inflammation and adjuvant-induced arthritis results in the reduction of the systemic clearance (Cltot.p), volume distribution (Vd,ss) and free fraction (fu). At the same time the area under the pharmacokinetic curve (AUC) increases and the half-life period (t1/2 beta) remains the same. In the phenobarbital-treated rats with acute inflammation Cltot.p increases, AUC and t1/2 beta decreased. Administration of cimetidine resulted in the opposite effect. In rats with adjuvant arthritis phenobarbital and cimetidine administration did not affect the propranolol elimination kinetics. In the phenobarbital-treated rats with inflammation Vd,ss significantly decreased and virtually did not change in cimetidine treated rats. The fu of propranolol increased markedly after the cimetidine treatment in all rats with inflammation, whereas phenobarbital treatment appeared effective only in rats with acute inflammation. The tissue-to plasma concentration ratio (Kp) of propranolol decreased in the liver of rats both with acute and chronic inflammation, whereas in the heart the effect was observed only in rats with chronic inflammation. The tissue to plasma concentration ratio of unbound propranolol (Kpu) decreased only in the liver of rats with acute inflammation. In the phenobarbital-treated rats with adjuvant arthritis Kp of propranolol in the liver increased and in the heart decreased, whereas cimetidine-treatment did not change Kp of propranolol in heart and decreased it in the liver. The Kpu of propranolol decreased only in the heart of rats with acute inflammation after phenobarbital treatment, whereas after cimetidine administration this parameter decreased in the heart and in the liver of rats regardless of the character of inflammation.

[The relationship between antipyrine kinetics, the seromucoid content and the xanthine oxidase activity in the plasma of rats with acute and chronic inflammation]. / Izuchenie sviazi mezhdu kinetikoi antipirina, soderzhaniem seromukoida i aktivnost'iu ksantinoksidazy v plazme krys s ostrym i khronicheskim vospaleniem.

The relationship between changes in seromucoid levels, xanthine oxidase activity in plasma, and drug metabolism in rats with turpentine-induced inflammation and adjuvant-induced arthritis was studied. For antipyrine, systemic clearance decreased, the volume distribution remained the same, and the half-life increased in turpentine- and adjuvant-treated rats. In both cases seromucoid level and xanthine oxidase activity in plasma increased. Treatment of rats with dexamehasone before turpentine-induced inflammation raised the level of seromucoid. However, dexamehasone treatment of rats with adjuvant disease significantly decreased the level of seromucoid. Moreover, dexamehasone administration did not significantly protect against the effects of inflammation on the hepatic microsomal drug-metabolizing enzyme system and activity of xanthine oxidase in plasma. Thus, pharmacokinetics of different drugs can significantly change in some types of inflammation in animals and humans, particularly by dexamehasone administration.