Биоэквивалентность бисопролола, таблетки покрытые оболочкой 10 мг АО «Химфарм», Республики Казахстан

Within the cross, a single, open, randomized study with 10 day washout period, the two sequences has been studied bioequivalence of tablet forms two bisoprolol 18 volunteers (10 mg dosage). Plasma samples were analyzed by a validated HPLC-MS/MS within 48 hours. For preparations analyzed following pharmacokinetic parameters were calculated: AUC0-t, Cmax, Tmax , Cmax /AUC. 90% confidence interval for log-transformed values for AUC0-t was 0.9142—1.0568 for Cmax —0,9371 —1,0473. The study concluded that comparable drugs were bioequivalence of bisoprolol.В рамках перекрёстного, однократного, открытого, рандомизированного исследования с 10 дневным периодом отмывки, с двумя последовательностями была изучена биоэквивалентность двух таблетированных форм бисопролола на 18 добровольцах (дозировка 10 мг). Образцы плазмы крови анализировали валидированным методом ВЭЖХ-МС/МС в течение 48 часов. Для анализируемых препаратов рассчитаны следующие фармакокинетические параметры: AUC0-t, Cmax, tmax, Cmax/AUC. 90% доверительный интервал для логарифмически преобразованных значений для AUC0-t составил 0,9142 — 1,0568 и для Cmax — 0,9371 — 1,0473. По результатам исследования был сделан вывод о биоэквивалентности сравниваемого препарата бисопролола

Оценка биоэквивалентности двух таблетированных форм лизиноприла на здоровых добровольцах

Under cross, single, open, randomized trial with 1 week washout period, with two sequences of 18 volunteers studied bioequivalence coated tablets, two manufacturers of lisinopril (20 mg dose). The concentration of lisinopril in the plasma samples was determined using HPLC with fluorimetric detection within 72 hours for the investigated preparations the following pharmacokinetic parameters were calculated:AUC0-∞, Cmax, tmax, Cmax/AUC. 90% confidence interval relations AUC0-∞ compared drugs totaled 0.8520 — 1.2102 for Cmax — 0,9288 — 1,1451. In addition to the 90% confidence intervals, analysis of variance revealed no statistically significant differences between the studied drugs. Concluded bioequivalence compared drugs lisinopril.В рамках перекрёстного, однократного, открытого, рандомизированного исследования с периодом отмывки 1 неделя, с двумя последовательностями на 18 добровольцах изучена биоэквивалентность таблеток, покрытых оболочкой, лизиноприла двух производителей (доза 20 мг). Концентрацию лизиноприла в образцах плазмы крови определяли методом ВЭЖХ с флуориметрическим детектированием в течение 72 ч. Для исследуемых препаратов рассчитаны следующие фармакокинетические параметры: AUC0-∞, Cmax, tmax, Cmax/AUC. 90% доверительный интервал отношений AUC0-» сравниваемых препаратов составил 0,8520 — 1,2102 и для Cmax — 0,9288 — 1,1451. В дополнение к 90% доверительным интервалам, дисперсионный анализ не выявил статистически значимых различий между изучаемыми препаратами. Сделан вывод о биоэквивалентности сравниваемых препаратов лизиноприла

Исследование сравнительной биоэквивалентности препаратов Пиоглитазон таблетки, 20 мг (АО «Химфарм», Республика Казахстан) и Актос® таблетки, 30 мг («Eli Lilly Holdings, Takeda Global Research and Development Centre Europe Ltd»)

Within the cross, a single, open, randomized study with a two-week washout period, the two sequences has been studied bioequivalence of tablet forms two pioglitazone 18 volunteers (30 mg dosage). Plasma samples were analyzed by a validated HPLC-MS/MS within 48 hours. Analyzed for drugs following pharmacokinetic parameters were calculated: AUC0-t, Cmax, tmax, Cmax /AUC. 90% confidence interval for log-transformed values of AUC0-t was 0.945 — 1.066 and Cmax — 0,871 — 1,044. The study concluded that bioequivalence compared pioglitazone drugs.В рамках перекрёстного, однократного, открытого, рандомизированного исследования с двухнедельным периодом отмывки, с двумя последовательностями была изучена биоэквивалентность двух таблетированных форм пиог-литазона на 18 добровольцах (дозировка 30 мг). Образцы плазмы крови анализировали валидированным методом ВЭЖХ-МС/МС в течение 48 часов. Для анализируемых препаратов рассчитаны следующие фармакокинетические параметры: AUC0-t, Cmax, tmax, Cmax/AUC. 90% доверительный интервал для логарифмически преобразованных значений AUC0-t составил 0,945 — 1,066 и для Cmax — 0,871 — 1,044. По результатам исследования был сделан вывод о биоэквивалентности сравниваемых препаратов пиоглитазона

The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia

Schizophrenia (Sch) is a severe and widespread mental disorder. Antipsychotics (APs) of the first and new generations as the first-line treatment of Sch are not effective in about a third of cases and are also unable to treat negative symptoms and cognitive deficits of schizophrenics. This explains the search for new therapeutic strategies for a disease-modifying therapy for treatment-resistant Sch (TRS). Biological compounds are of great interest to researchers and clinicians, among which D-Serine (D-Ser) and D-Aspartate (D-Asp) are among the promising ones. The Sch glutamate theory suggests that neurotransmission dysfunction caused by glutamate N-methyl-D-aspartate receptors (NMDARs) may represent a primary deficiency in this mental disorder and play an important role in the development of TRS. D-Ser and D-Asp are direct NMDAR agonists and may be involved in modulating the functional activity of dopaminergic neurons. This narrative review demonstrates both the biological role of D-Ser and D-Asp in the normal functioning of the central nervous system (CNS) and in the pathogenesis of Sch and TRS. Particular attention is paid to D-Ser and D-Asp as promising components of a nutritive disease-modifying therapy for TRS

Therapeutic and Toxic Effects of Valproic Acid Metabolites

Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: β-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient’s pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine)

Therapeutic and Toxic Effects of Valproic Acid Metabolites

Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: β-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient’s pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine)

The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic

Background:. High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods:. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results:. Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations:. Cross-sectional survey, preponderance of non-representative participants. Conclusions:. Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics

Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT – www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6–18 months plus 24–36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14–17 years), and children (age 6–13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents’ and families’, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth

Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology “P-score”. Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1–4 items (“COH-FIT items”) were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health

The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic.

. High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. . Cross-sectional survey, preponderance of non-representative participants. . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics