Review of bioequivalence studies of cholecalciferol drugs

Introduction: The general requirements for assessing bioequivalence of endogenous drugs are described in the relevant guidelines, but they do not provide a complete picture of how to adequately develop a design of such a study. The aim of this article is to offer recommendations on the development of a design for bioequivalence studies of endogenous drugs, using cholecalciferol as an example. Materials and methods: A systematic review of our database on the results of bioequivalence studies of generic drugs revealed one study of cholecalciferol drugs, which was performed using a simple cross-over design. The study involved 24 healthy adult subjects. The data of 24 volunteers were retrospectively analyzed to identify endogenous cholecalciferol concentrations and intraindividual variability (CVintra) for Cmax and AUC0-t. As part of a retrospective analysis, we also assessed gender differences of pharmacokinetics. Results and discussion: Assessment of the bioequivalence of cholecalciferol drugs was complicated by the presence of endogenous concentrations of cholecalciferol for the tested drug – 1.27 (±0.55) ng/ml and for the reference drug – 0.98 (±0.55) ng/ml. The results of the analysis of the intraindividual variability of Cmax and AUC0-72 of the tested and reference drugs showed the following CVintra values – 22.80% and 21.58%, respectively. A comparative analysis of pharmacokinetic parameters did not reveal statistically significant gender differences. The article presents approaches to the planning of future bioequivalence studies of cholecalciferol drugs. Conclusion: Cholecalciferol is not a highly variable drug; however, it relates to drugs – analogues of endogenous compounds, which requires determining the endogenous concentrations.

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lanning and Evaluation of Bioequivalence Studies of Telmisartan Generic Drug Products

Drug development & registration ◽

10.33380/2305-2066-2019-8-3-101-106 ◽

2019 ◽

Vol 8 (3) ◽

pp. 101-106

Author(s):

A. L. Khokhlov ◽

D. P. Romodanovsky ◽

A. E. Miroshnikov

Keyword(s):

Confidence Interval ◽

Generic Drug ◽

Generic Drugs ◽

Intraindividual Variability ◽

Pharmacokinetic Parameters ◽

Key Factors ◽

Limit Of Quantification ◽

Optimal Method ◽

Reference Drug ◽

Upper Limit

Introduction. Telmisartan is a modern antihypertensive drug, from the group of angiotensin II receptor antagonists, which, recently, has been the purpose of the development and registration of generic drug. The pharmaceutical development of telmisartan generics and their evaluation in bioequivalence studies is complicated by many factors that influence the results of comparison with the reference drug. Therefore, it is relevant to study these factors for the proper planning of studies and for evaluating their results from the generic drugs of telmisartan.Aim. The aim of the study is to identify the key factors that should be considered in planning and evaluation of bioequivalence studies of telmisartan’s generics.Materials and methods. To identify the key factors influencing the planning and evaluation of studies of telmisartan generics, a retrospective analysis of the results of seven telmisartan studies was conducted. Calculated pharmacokinetic parameters Cmax, AUC0-t, tmax; their average values; the values of intraindividual variability for each study and the average of the coefficients of intraindividual variability obtained.Results and discussion. The results of the study demonstrated that the drugs of telmisartan are highly variable, there are sex differences in the pharmacokinetics of telmisartan. According to the averaged values of the concentrations and pharmacokinetic profiles of telmisartan, the following areas were determined: the area of maximum exposure of telmisartan, the duration and schedule of blood sampling, to obtain the optimal pharmacokinetic profile. The most optimal method for the determination of telmisartan is HPLC MS/MS with a lower limit of quantification in the range of 0.5–3 ng/ml. The upper limit of the 90% confidence interval was calculated for the pooled average of the coefficients of intraindividual variability obtained in the considered studies.Conclusion. Recommendations were developed for planning and evaluating bioequivalence studies of generic telmisartan preparations. It is necessary to plan bioequivalence studies with replicated design in three or four periods, with two crossovers, with two sequences of drug intake. To assess the pharmacokinetics of telmisartan one should use the data on its exposure given in the article. When determining the sample size, one should be guided by the upper limit of the confidence interval of the averaged values of the coefficient of intra-individual variability Cmax of telmisartan (45%). Evaluation of results should be carried out taking into account the possibility of scaling bioequivalence limits for the Cmax. The bioequivalence limit for the AUC0-t parameter should remain in the range of 80.00–125.00%, as well as the ratio of geometric means for both parameters.

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Agrarian receipts as a tool for the structural transformation of financial and credit relations in the agrarian business of the region

Problems of Innovation and Investment Development ◽

10.33813/2224-1213.18.2019.5 ◽

2019 ◽

pp. 40-53

Author(s):

Yuliia Nehoda

Keyword(s):

Comparative Analysis ◽

Retrospective Analysis ◽

Structural Transformation ◽

Pilot Project ◽

Bank Lending ◽

Economic Benefits ◽

Advantages And Disadvantages ◽

New Instrument ◽

Agricultural Business ◽

Business Entities

The subject of the research – is a set of organizational-economic relations arising in the process of structural transformation of financial and credit relations in the agricultural business. The purpose of the article is a retrospective analysis of structural transformations of financial and credit relations in the agricultural business, evaluation of the effectiveness and feasibility of the introduction of agricultural receipts as a new instrument of lending to the agricultural business of the regions. Methodology of work – system-structural and comparative analyzes (to determine the effectiveness of the crediting mechanism according to the agricultural receipts of the farmers of the region); monographic (when studying the problems of the functioning of the mechanism of lending to agrarians by agrarian receipts) economic analysis (when carrying out a comparative analysis of the mechanism of classical bank lending to the agrarian business and the mechanism of lending to agrarians according to agrarian receipts); modeling and forecasting (when determining ways to overcome the existing deficiencies in the mechanism of lending to agrarian business entities of the region according to agrarian receipts). The results of the work – a retrospective analysis of the structural transformation of financial and credit relations in the agricultural business was carried out. The mechanism of crediting agrarians according to agrarian receipts and the scale of its distribution in the agrarian business of the region are considered. A comparative analysis of the mechanism of classical bank lending to the agrarian business and the mechanism of lending to agrarians according to agrarian receipts was carried out. In the framework of the pilot project “Agrarian receipts in Ukraine” of the international financial corporation (IFC) in partnership with the Swiss Confederation in Ukraine, the example of the Poltava region defined the effectiveness of the crediting mechanism according to the agrarian receipts of the agrarians of the region. The advantages and disadvantages of the mechanism of crediting the subjects of the agrarian business on agrarian receipts are noted. The ways to overcome the existing shortcomings of the mechanism of crediting the subjects of the agrarian business of the region according to agricultural receipts are determined. Conclusions – according to the results of the conducted research, the effectiveness of the mechanism of lending to the agricultural business of the regions according to agricultural receipts was proved, its advantages and disadvantages were noted, and attention was also focused. Proposed in Art. 7 of Law No. 5479-VI clearly delineate cases and restrictions on the debtor’s reimbursement of expenses incurred by the lender with the acquisition of the right to grow and harvest the pledged crop of agricultural products, which will ensure the principle of equality of parties on economic benefits and distribution of credit risks according to agricultural receipts.

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