Репозиторий Университета

Background High values of endogenous levels of magnesium (Mg) in the body and mechanisms of homeostasis regulation make it difficult to assess the bioavailability of these drugs. The aim of this study was to assess the Mg concentration in blood in volunteers and in erythrocytes in patients with hypomagnesemia. Methods The study included 20 healthy volunteers and 62 patients with chronic heart failure (CHF) I-III functional class (FC) NYHA classification. We studied the composition of Mgorotate and Mgorotate plus potassium (К)orotate. Blood sampling was carried out at 8 a.m. and within 10 h after administering the drugs. Measurement of Mg pharmacokinetic parameters: AUC (concentration of the active substance-time), and Cmax (maximum concentration) in volunteers and measurement of the concentration of Mg in erythrocytes of patients. Results The results indicated that both the AUC in volunteers and concentration of Mg in erythrocytes of patients are comparable, and the differences are not statistically significant. Conclusions The study showed that the standard method of calculating the AUC (total serum Mg) is insufficient for comparative evaluation of Mg absorption due to the high levels of its endogenous content and a small increase in concentration after taking the drugs. It is advisable to assess the concentration of Mg in the red blood cells of patients.

© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston. Calcium drugs are analogs of endogenous substances. The baseline concentration of endogenous substances in the body and homeostasis mechanisms of regulation make the bioavailability and bioequivalence (BE) evaluation of these drugs very difficult. The aim of the study was to assess the pharmacokinetic parameters of calcium in the studies of comparative bioavailability combined with the assessment of homeostatic regulation mechanisms. The study included 42 healthy male volunteers. We studied the composition of 1000 and 1200 mg of calcium, and 800 and 1000 IU of cholecalciferol. Blood sampling was carried out at 8 a.m. and 0.5, 1, 2, 3, 4, 6, 8 h after administering the drugs. Calcium pharmacokinetic parameters were measured: the area under the curve (AUC) "concentration-time", and maximum concentration (Cmax) in volunteers. The excretion of calcium in urine in terms of creatinine clearance and parathyroid hormone (PTH) levels was assessed. The maximum excretion of calcium was converted to creatinine (calcium/creatinine). Enzyme-linked immunosorbent assay (ELISA) was used to determine the PTH and the o-cresolphthalein method to quantitatively measure the total calcium serum and urine. Results indicated that both the AUC and the excretion of calcium are comparable, and the differences are not statistically significant, p>0.05 (the ratio of calcium and creatinine in the urine maintained within physiological levels). The comparable dynamics of PTH concentration is an indirect measure of the amount of absorbed calcium. The study demonstrates that, along with the standard way of calculating the area under the curve "concentration-time" (total calcium in serum), it is important to assess the calcium excretion in urine in terms of creatinine excretion, as well as focusing on the changes in the PTH levels in volunteers, which could be considered as a marker of the calcium level in the blood.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Issues pertaining to determination of the pharmacokinetic parameters of calcium preparations are examined using their comparative bioavailability as an example. Pharmacokinetic parameters of calcium such as area under the concentration—time curve (AUC) and maximum concentration (Cmax) are calculated considering the background calcium contents in volunteers. Calcium excretion with urine is assessed as clearance of creatinine, a calcium elimination factor. The dynamics of the content of parathormone (PTH), the main hormone regulating calcium homeostasis, are studied. The results can be used to plan clinical trials for assessing the pharmacokinetics of drug analogs of endogenous compounds.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Results of studying the comparative bioavailability of pharmaceutical preparations - alternative analogs of endogenous compounds containing calcium and colecalciferol are presented. The drug concentrations were recalculated with allowance for the endogenous calcium level, in accordance with the relevant normative guidelines. The standard methodology of bioequivalence studies can be used to evaluate the quality of reproduced calcium preparations, taking into account low values of intra-individual variability of pharmacokinetic parameters.