Retrospective Analysis of Experimental and Clinical Studies of Flakozid in Viral Hepatitis

• Published in: Razrabotka i registraciâ lekarstvennyh sredstv (Online) Vol. 10; no. 4; pp. 169 - 176
• Main Authors: Karabaeva, V. V., Krepkova, L. V., Babenko, A. N., Bortnikova, V. V., Fateeva, T. V., Mizina, P. G., Mikheeva, N. S., Karabaeva, O. N.
• Format: Journal Article
• Language: English; Russian
• Published: LLC Center of Pharmaceutical Analytics (LLC «CPHA») 25-11-2021
• Subjects: "flakozid"; experimental and clinical studies; viral hepatitis a; viral hepatitis b; viral hepatitis c
• ISSN: 2305-2066; 2658-5049
• DOI: 10.33380/2305-2066-2021-10-4-169-176

Introduction.
Viral hepatitis (HV) by its socio-economic significance occupies one of the leading places in human infectious pathology, therefore, the development of fundamentally new methods of prevention, diagnosis and treatment, as well as the creation of new antiviral drugs remain relevant. An antiviral herbal drug "Flakozid" has been created in VILAR, which is presented in a dosage form – 0,1 g tablets for oral administration.
А
im.
To analyze the experimental and clinical efficacy and safety of flakozid therapy in viral hepatitis.
Materials and methods
. Experimental study of the effect of flakozid on viral hepatitis A (HAV). The AGMK cell culture (BS-C-1 line) and the hepatitis A virus strain HM 175 adapted to it were used in the work. The studies were conducted in two series of experiments using different concentrations of the drug, which was introduced into cultures simultaneously with the infection of HAV. Experimental study of the effect of flakozid on viral hepatitis C (HCV). In the present experiments, a virus-containing culture fluid collected from infected cultures of chicken embryo fibroblasts containing 7,0 lg TCD50/ml of infectious HCV (genotype 1b) was used. The cytotoxic, viricidal and antiviral activity of flakozid was studied using transplanted cultures of pig embryo kidney cells (SPEV) obtained from the collection of cell lines of the D. I. Ivanovsky Research institute of virology of the Ministry of Health of the Russian Federation. In the experiments, a one-day monolayer of cells grown in 96-well plastic culture panels was used. ID50 – the concentration of the drug "Flacozid", which inhibits the development of the virus in the monolayer by 50 %, and CD50 – its minimum concentration, which causes cytotoxic destruction of 50 % of the cells of the monolayer, as well as the CTI – chemotherapeutic index, calculated as the ratio of CD50 to ID50, were determined. A well – known domestic antiviral agent, "Ribavirin", was used as a comparison drug. Clinical studies of flakozid in viral hepatitis A. The results of clinical studies of the antiviral drug "Flakozid" (0,1 g tablets) were analyzed in 258 patients with viral hepatitis A. "Flakozid" was prescribed to patients with a moderate course of the disease, 0,1 g 3 times a day for 20 days against the background of basic therapy: diet, alkaline drinking, Enterodes®. The therapeutic effect was assessed by clinical (weakness, decreased appetite, nausea, vomiting) and biochemical parameters (the level of direct bilirubin, transaminase activity), as well as by the severity of hepatolienal syndrome. Clinical studies of flakozid in viral hepatitis В. The results of clinical studies of the antiviral drug "Flakozid"(0,1 g tablets) were analyzed in 410 patients with acute viral hepatitis B, which was regarded as moderate. "Flakozid" was prescribed against the background of basic therapy: diet and detoxification therapy: 5 % glucose solution, 5 % ascorbic acid solution, "Hemodesi", at a daily dose of 0,3–0,8 g for up to 38 days. The comparison group received the same basic therapy without flakozid. The dynamics of clinical symptoms (general weakness, headache, sleep disorders, dizziness, nausea, vomiting, impaired appetite, itchy skin, pain in the right hypochondrium, jaundice, etc.), data from laboratory examination methods were evaluated, markers of hepatitis B – HBeAg and Australian antigen (HBsAg) were determined every 10 days and indicators of cellular immunity before the appointment and after 21 days of treatment; the absolute number of lymphocytes, the total number of T-lymphocytes, as well as theophylline-resistant and theophylline-sensitive cells.
Results and discussion
. The results of experimental studies revealed the antiviral effect of flakozid against the hepatitis A virus, confirmed during clinical studies in adult patients. Treatment with flakozid in patients with viral hepatitis A against the background of basic therapy at a daily dose of 0,3 g for 20 days led to a significant reduction in the symptoms of intoxication, a reduction in the jaundice period, normalization of the size of the liver and spleen. Treatment with flakozid as part of complex therapy of patients with acute viral hepatitis B (AHVB) of moderate severity in daily doses of 0,3–0,8 g for 38 days showed its high effectiveness, contributing to a faster disappearance of clinical symptoms of the disease (improvement of the general condition of patients, reduction of the severity and disappearance of clinical symptoms of intoxication, reducing of the jaundice period), normalization of biochemical parameters (reducing the level of bilirubin and transaminase activity), as well as elimination of HBsAg from the blood, stimulation of cellular immunity. "Flakozid" was well tolerated, did not cause allergic reactions. Based on the results of clinical studies, "Flakozid" is approved for medical use as an antiviral agent (registration number 90/248/7). The high antiviral activity of flakozid against the hepatitis C virus in cell cultures was established. In terms of the severity of the therapeutic effect, "Flakozid" was not inferior to ribavirin, and in terms of CTI it was noticeably superior.
Conclusion.
Treatment with flakozid in patients with viral hepatitis A and B showed its high efficiency, contributed to a faster disappearance of clinical symptoms of the disease, normalization of biochemical parameters, elimination of HCV from the blood, good tolerability. "Flakozid" is recommended in clinical practice in the complex treatment of hepatitis A and B. In vitro experiments have established a high antiviral activity of flakozid against the hepatitis C virus, which justifies the possibility of conducting clinical studies of the drug in patients with the viral hepatitis C.