TY - JOUR AU - Shmatenko, O. P. AU - Davtyan, L. L. AU - Tarasenko, V. O. AU - Prytula, R. L. AU - Voronenko, D. V. AU - Drozdov, D. V. AU - Andriychuk, Ya. R. AU - Kozyko, N. A. PY - 2021/12/30 Y2 - 2024/03/28 TI - Kinetics (in vivo) release of active pharmaceutical ingredients from the drug under the conditional name AMO-sol JF - Ukrainian Journal of Military Medicine JA - UJMM VL - 2 IS - 4 SE - Military pharmacy DO - 10.46847/ujmm.2021.4(2)-130 UR - https://ujmm.org.ua/index.php/journal/article/view/239 SP - 130-139 AB - Introduction. Pharmacokinetics plays a significant role in pharmacy. Studies of the dependence of the reaction rate on various factors make it possible to intensify the technological processes for the manufacture of drugs. Pharmacokinetic studies related to the study of the rate of absorption and withdrawal of drugs from the body allow us to interpret the mechanisms of their physiological action. The final process begins with the release of the active pharmaceutical ingredients from the pharmaceutical system (aerosol), then the absorption and diffusion of the active substances to the absorption surface - the wound surface. The absorption process itself is also diffusion and depends on many factors: the amount, properties and physical state of the active substance, the total composition and properties of the aerosol, as well as technological factors and the physiological state of the absorption surface (the first stage of the wound process).The purpose is to conduct in vivo pharmacokinetic studies to isolate and detect benzocaine and miramistin in the blood of rats using a single-chamber pharmacokinetic model.Materials and methods. During experimental studies, the materials were active pharmaceutical ingredients – ofloxacin, benzocaine, miramistin, as well as auxiliary substances – sodium carboxymethyl cellulose, methylcellulose, polyvinyl alcohol, polyvinyl pyrolidone, propylene glycol, glycerol, polyethylene oxide-400, ethyl alcohol, citric acid monohydrate, chladon-134a. In vitro methods established the order of the kinetic reaction to select a model for determining pharmacokinetic parameters by the in vivo method. The pharmacokinetic parameters of AMO sol were examined in the blood of white Wistar rats after its disposable application to a model wound. The isolation of active pharmaceutical ingredients (benzocaine, miramistin) was carried out using the Agilent chromato-mass spectrometer 6850/5973N manufactured by Agilent Technologies, a quartz capillary column NR-5MS 0.25 mm x 30 m. Temperature: injector – 250 0С, mass spectrometer interface (Transfer line) – 280 0С, ion sources – 230 0С, quadruplets – 150 0С. Ionization mode – electron shock, electron energy – 70 eV, electric multiplier voltage – 106 V more than at Autotune. Scan range 40 – 550 a.o.m. Thermostat temperature programming mode: 90 0С – 2 min. Then it rises to 300 0С at a rate of 20 0С /xv, and holds at this temperature 10 min. Carrier gas speed (helium) – 1,0 ml/min. Sample input mode – 2 mcL without flow separation.Results. A single-chamber pharmacokinetic model was used to perform in vivo pharmacokinetic studies to isolate and detect benzocaine and miramistine in the blood of rats. The calculated values of the ke and ka constants showed that the application of drugs to the tissues of test rats is an example of a flip flop phenomenon, since the elimination rate constant is greater than (0,022 1/min) the absorption rate constant (0,007 1/min), and changes its position with respect to the time tmax, which corresponds to the equality of the parameters of the elimination and absorption rates. It was determined that when LS containing 12,5 μg/x benzocaine and 1,25 μg/x miramistin were administered, the maximum blood concentration (0,052 μg/ml) was observed for benzocaine after 30 minutes and 0,072 μg/ml after 240 minutes for miramistin. The clearance for benzocaine is calculated to be 0,00011 ml/( khv‧g) and for miramistin to be 0,000112 ml/( min g), respectively. In clinical settings, clearance serves to calculate the dose necessary to maintain an equilibrium concentration of drugs in the blood, that is, a maintenance dose. The volume of distribution is determined, which serves to calculate the loading dose of the preparation, which is necessary to achieve its desired concentration in the blood. For this model, the volume of drug distribution in the body for both benzocaine and miramistin is 0,005 ml/h, respectively. The final stage of in vivo studies using a single-chamber pharmacokinetic model was the determination of the half-life. In one period, 50 % of drugs is excreted from the body, in two – 75 %, in three – 90 %. Thus, the half-life of benzocaine at the elimination rate is 30,904 minutes, and at the suction rate – 98,18 minutes. The half-life of miramistin at the elimination rate is 30.942 minutes, and at the suction rate – 92,821 minutes. Therefore, in pharmacokinetic studies, the above parameters are used to evaluate changes in the concentration of drugs over time in a specific chamber where the desired therapeutic effect of the drug is obtained.Conclusions. In vivo studies were conducted using a single-chamber pharmacokinetic model to isolate and detect benzocaine and miramistin in the blood of rats. It is proved that the developed drugs show predominantly local action, since at this moment the flow of release of active substances from the aerosol is greater than the flow of penetration through the natural biological barriers of the body. Qualitative evaluation of pharmacokinetic process with establishment of 15 pharmacokinetic parameters was carried out. ER -