Principles of Statistical Evaluation of Bioequivalence Studies in the Context  of Current Regulatory Requirements and Legal Acts

Ромодановский, Д. П.; Горячев, Д. В.; Соловьева, А. П.; Eremenko, N. N.

doi:10.30895/1991-2919-2018-8-2-92-98

Cited by 5 publications

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“…Согласно данным литературы, лекарственные средства с пресистемным метаболизмом часто демонстрируют высокую внутрииндивидуальную вариабельность в исследованиях биоэквивалентности, что осложняет их оценку [3,4]. Высокая внутрииндивидуальная вариабельность определяется на основании остаточной вариабельности после дисперсионного анализа (Analysis of variance (ANOVA)), выраженной в среднеквадратичной ошибке (MSE) [5][6][7]. Высоковариабельными считаются препараты с MSE более 0,0862 (коэффициент внутрииндивидуальной вариабельности (CV intra ) более 30%):…”

Section: оригинальные статьи / Original Articlesunclassified

Expert Approaches to the Assessment of Losartan Drugs Bioequivalence

Ромодановский¹,

Горячев²

2020

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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Angiotensin II receptor antagonists (ARAs) are one of the most promising classes of antihypertensive drugs. They are most widely represented on the Russian market by losartan drugs which total 24 items. Therefore, it is crucial to analyse the factors that may affect the results of comparison of generic and reference losartan drugs.The aim of the study was to perform a retrospective analysis of bioequivalence studies of generic losartan drugs in order to develop approaches to expert evaluation of research protocols and reports.Materials and methods: the retrospective analysis covered the results of 27 bioequivalence studies of losartan and included the calculation of the pharmacokinetic parameters Cmax and AUC0-t, their intra-individual variability, and the weighted average of intra-individual variability. The calculations were made for the pooled population of men and women, as well as separately for each gender.Results: the data obtained indicate borderline high variability of losartan in bioequivalence studies (for Cmax in 50 % of the studies). It was demonstrated that losartan drugs may have different pharmacokinetics in men and women in terms of Cmax and AUC0-t. The retrospective analysis of the data made it possible to formulate relevant expert approaches to evaluation of protocols and reports of bioequivalence studies of losartan drugs.Conclusions: Bioequivalence of losartan should be evaluated in three- or four-period, double crossover, two-sequence replicate design studies. The study has to determine the pharmacokinetic parameters of the starting compound and its active metabolite; the period of determination of analytes should be at least 36 hours; the washout period of 7 days is sufficient; blood sampling should be more frequent during the first hour after administration for losartan and during the first 3–4 hours for the metabolite. When determining the sample size, the weighted average of the coefficient of intra-individual variability of Cmax of losartan (33 %) should be taken into account. The bioequivalence margins for Cmax can be scaled up.

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Section: оригинальные статьи / Original Articlesunclassified

Expert Approaches to the Assessment of Losartan Drugs Bioequivalence

Ромодановский¹,

Горячев²

2020

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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“…на трех важнейших компонентах взаимозаменяемости: терапевтической, фармацевтической эквивалентности и фармакокинетической биоэквивалентности. Для доказательства чего, как правило, необходимо проведение дополнительных клинических исследований [3][4][5][6][7].…”

Section: обзоры / Reviewsunclassified

“…Большинство ПЭП -препараты с узким терапевтическим диапазоном, поэтому при проведении исследования следует использовать стандартный двухпериодный перекрестный дизайн в двух группах и двух последовательностях. Также возможно применение полного репликативного (повторного) дизайна исследования в двух последовательностях [5].…”

Section: методологические подходы к проведению клинических исследованunclassified

New Anticonvulsants: Interchangeability Issues and the Use of Generic Anticonvulsants in Clinical Practice

Архипов¹,

Сокова

Городецкая

et al. 2019

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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This article looks into interchangeability and therapeutic equivalence of innovator and generic anticonvulsants — the first-generation and new antiepileptic drugs (AEDs). The results of a number of clinical trials assessing therapeutic equivalence of generic AEDs support the opinion that these medicines could only be substituted provided an ultra-cautious approach is used, even if the case involves only one International Nonproprietary Name, including, but not limited to different dosage forms of one and the same product. The aim of the study was to analyse factors leading to incorrect assessment of therapeutic equivalence of new and generic anticonvulsant drugs, and to improve methodological approaches to conducting clinical trials of these products. The paper cites data from Russian and foreign sources which state that the substitution of AEDs in some patients in full remission may result in adverse reactions or relapse of seizures. The analysis of the experience of scientific, expert, and regulatory institutions made it possible to develop a course of actions to be used when substituting AEDs and conducting clinical trials that assess therapeutic equivalence of new and generic anticonvulsants. The proposed methodology will help minimise potential health risks brought about by various factors that result in incorrect assessment of AEDs therapeutic equivalence and interchangeability.

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Selection of Adaptive Designs in Studies of Bioequivalence. Decision Criteria

Eremenko,

Goryachev

2023

Pharm Chem J

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Principles of Statistical Evaluation of Bioequivalence Studies in the Context of Current Regulatory Requirements and Legal Acts

Cited by 5 publications

References 0 publications

Expert Approaches to the Assessment of Losartan Drugs Bioequivalence

Expert Approaches to the Assessment of Losartan Drugs Bioequivalence

New Anticonvulsants: Interchangeability Issues and the Use of Generic Anticonvulsants in Clinical Practice

Selection of Adaptive Designs in Studies of Bioequivalence. Decision Criteria

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