The pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in the rat blood plasma after different routes of administration was studied. The drug was administered at dose of 150 mg/kg by single and repeatedly. After single intravenous and intraperitoneal injection, GC-2 was detected for 2 h, its half-life was 0.4 h. GC-2 absolute bioavailability after single intraperitoneal injection was 84.62 %, that indicates the prospect of development its injectable (intramuscularly) dosage form. After 4-fold (1.5 h dosing interval) intraperitoneal injection dose-independent pharmacokinetic parameters of GC-2 practically do not change compared to single administration. This indicates that GC-2 is not accumulated in the body of rats. The hypothesis of the linearity of the pharmacokinetics of GC-2 in the rats blood plasma after single intraperitoneal administration at doses of 50, 100 and 150 mg/kg was tested. It was found that the kinetics of GC-2 in the rat blood plasma is linea.

The pharmacokinetics of a new potential cardioprotective agent ALM-802 was studied in rats after single intravenous and intragastric administration at doses of 10 and 100 mg/kg, respectively. The absolute bioavailability was 4.45 %, which indicates the potential for the development of a dosage form for oral administration

We studied the pharmacokinetics of GZK-111 (N-phenylacetyl-glycyl-L-proline ethyl ether), a compound with neuroprotective activity, and its metabolite CPG (cyclo-L-prolylglycine) in rat blood plasma after single intravenous and intragastric administration in a dose of 20 mg/kg. It was found that the parent drug undergoes intensive biotransformation; its metabolite CPG persists in the circulation more than twice as long as GZK-111 and its plasma concentrations were higher by 50-70 times than the concentrations of the parent compound.

GIZh-298 is a new derivative of 4-phenylpyrrolidone with anticonvulsant and nootropic effects. A selective and sensitive HPLC-MS technique for the quantitative determination of GIZh-298 in rat blood plasma has been developed and validated. The linearity of the technique was confirmed by a high correlation coefficient (>0.99). Recovery of GIZh-298 from blood plasma averaged 73.4 ±3.4 %. Accuracy during one working cycle and between cycles was < 4.01%, precision < 8.03 %. The study of the stability of GIZh-298 revealed that the target compound is stable in a biomatrix at room temperature (4 h), when it is in a thermostatically controlled autosampler (8 °C) during an analytical experiment, with prolonged storage at -50 ° C for 30 days, and also if it is subjected to several freeze-thaw cycles (3 cycle). The pharmacokinetics of GIZh-298 in rat blood plasma after a single intravenous injection at a dose of 60 mg/kg was studied.

Metabolism of a new neuroprotector GZK-111 ( N -phenylacetylglycyl- L -proline ethyl ester) in rat blood plasma was studied by HPLC-mass spectrometry. Four biotransformation products were identified. It is concluded that the main ways of GZK-111 biotransformation are hydrolysis of the ester bond by esterases followed by degradation of the resulting metabolite, as well as reactions leading to the formation of phenylacetic acid and cycloprolylglycine that exhibits neuropsychotropic activity.

GIZh-290 is a new derivative of 4-phenylpyrrolidone, based on the structures of racetams that combine anticonvulsant and nootropic effects. The method of high-performance liquid chromatography with mass spectrometric detection was developed and validated for the quantitative determination of a new potential anticonvulsant compound GIZh-290 in rat blood plasma. For the extraction of the analyte, liquid-liquid extraction with diethyl ether was used. The method was validated based on its selectivity, linearity, accuracy, precision, and stability. The linearity of the method was confirmed by a high correlation coefficient of 0.999. The percent recovery of GIZh-290 from blood plasma was 79.2 %. The intra- and inter-batch accuracy were 19.32 and 12.14 %. It was found that blood plasma samples containing GIZh-290 can be stored at ambient temperature during the working day.

We studied the pharmacokinetics of a drug preparation, ethyl ester of N-phenylacetyl-glycyl-L-proline, exhibiting neuroprotective activity and its metabolite cyclo-L-prolylglycine in rat blood plasma after a single intravenous administration at a dose of 20 mg/kg. The metabolite was found to circulate in the systemic bloodstream of animals twice as long as the ethyl ester of N-phenylacetyl-glycyl-L-proline, with its plasma concentrations being 50–70 times higher than those of the parent compound.

На крысах изучена фармакокинетика соединения IPAC-2015. После однократного внутрижелудочного введения в дозе 30 мг/кг исследуемое вещество в организме крыс определяется на протяжении 24 ч. Период полувыведения IPAC-2015 составил около 11 ч. Показано, что тканевая доступность IPAC-2015 в хорошо васкуляризированных органах (печень, почки, селезенка) значительно выше, чем в скелетной мускулатуре. В органе-мишени — головном мозге — данный показатель составил 0,61. Абсолютная биодоступность соединения IPAC-2015 у крыс составила 27,54 %.

На кроликах изучена фармакокинетика и определена относительная биодоступность нового фармакологического вещества, обладающего нейропротекторным действием — соединения DF-302 (5-[2-(5-фторпирид-3-ил)этил]-2,8-диметил-2,3,4,5-тетрагидро-1H-пиридо[4,3-b]индола дигидрохлорид) после его однократного, перорального введения в виде субстанции и таблеточной массы. Концентрации DF-302 оценивали в плазме крови с использованием ВЭЖХ с масс-спектрометрическим определением. Биодоступность соединения DF-302 из таблеток в сравнении с субстанцией составила (121,37 ± 25,02) % (p ≤ 0,05).

The review discusses relationships between pharmacokinetic parameters and effects of psychotropic drugs, both in preclinical studies and clinical practice. The identification of such correlations can serve as a basis for understanding the complex system of relationships between pharmacokinetic and pharmacodynamic mechanisms in the manifestation of the action of this group of drugs and allows us to use the data of pharmacokinetic studies to optimize therapeutic approaches in medical practice.

The role of cytochrome P450 isoforms CYP2C9 and in the metabolism of losartan described. Losartan pharmacokinetics data in humans and laboratory animals are presented. Examples of drug-drug interactions of substrate marker losartan of CYP2C9 of with different drugs are given. The results of studies of the effects of afobazole, an inducer (rifampicin) and inhibitors (fluconazole) in effective doses on the pharmacokinetics of losartan.

The pharmacokinetics of the nerve growth factor mimetic GK-2 (dimeric dipeptide mimetic of the 4-th loop NGF, a derivative of fluoro-substituted 5-[2-(5-fluoropyrid-3-yl) -ethyl)]-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole) in rabbits after a single intravenous injection of an injectable dosage form at dose 24 mg (7,8-8,7 mg/kg). GK-2 concentrations in the blood plasma were determined by high-performance liquid chromatography with massspectrometric detection. GK-2 can be attributed to "short-lived" drugs, since the half-life from the rabbits blood plasma was 0.9±0.1 h.

The technique of quantitative determination of GZK-111 and CPG compounds in rat blood plasma has been developed. The analysis was carried out using the combined method of high-performance liquid chromatography with mass spectrometric detection. The method was linear in the concentration range of 25-1000 ng/ml for both compounds. Percentage of GZK-111 extraction from rat blood plasma was 57.8 %. The lower limit of detection for GZK- 111 compound was 25 ng/ml. Percentage of extraction of CPG compound was 42.5 %. The lower limit of detection of CPG compound was also 25 ng/ml.

На аутбредных крысах изучена фармакокинетика соединения DF-302, обладающего нейропротективным действием, при разных способах введения. После однократного внутрижелудочного введения в дозе 25 мг/кг в организме крыс DF-302 определялся на протяжении 8 ч. Период полувыведения исследуемого соединения составил около 1,5 ч. Показано, что тканевая доступность (fТ) DF-302 в хорошо васкуляризированных органах (печень, селезенка, почки) в десятки раз выше, чем в скелетной мускулатуре крыс (18,65; 6,09; 1,56 в сравнении с 0,19). В органе-мишени — мозге — fТ составила 0,17. Абсолютная биодоступность соединения DF-302 составила 8,72 %, что свидетельствует о потенциальной возможности разработки лекарственной формы для приема внутрь.