Clinical safety and pharmacokinetic evaluation of aqueous extract of an anti-viral phytopharmacetical drug as a potential for the treatment of dengue and COVID-19.

Background And Aim: Dengue a worldwide concern for public health has no effective vaccine or drug available for its prevention or treatment. There are billions of people who are at risk of contracting the dengue virus (DENV) infections with only anti-mosquito strategies to combat this disease. Based on the reports, particularly in vitro studies and small animal studies showing anti-viral activity of aqueous extract of (AQCH), studies were conducted on AQCH tablets as a potential for the treatment of dengue and COVID-19 infections. The current study was part of the research on AQCH tablet formulation and was aimed to evaluate safety and pharmacokinetics in healthy human subjects.

Materials And Methods: Sixty healthy adult human subjects were divided into 5 groups (cohorts: I to V; n = 12 per cohort) and randomized in the ratio of 3:1 to receive active treatment or placebo in a blinded manner. Five doses 100 mg, 200 mg, 400 mg, 600 mg and 800 mg tablets were administered three times daily at an interval of 8 h for days 01-09 under fasting conditions and a single dose in morning on day 10. Safety assessment was based on monitoring the occurrence, pattern, intensity, and severity of adverse events during study period. Blood samples were collected for measurement of the bio-active marker Sinococuline concentrations by a validated LC-MS/MS method followed by pharmacokinetic evaluation.

Results And Conclusion: The test formulation was well tolerated in all cohorts. Sinococuline peak plasma concentration (C) and total exposure of plasma concentration (AUC) demonstrated linearity up to 600 mg and saturation kinetics at 800 mg dose. There was no difference observed in elimination half-life for all the cohorts, suggesting absence of saturation in rate of elimination. Dose accumulation was observed and steady state was achieved within 3 days. The information on human pharmacokinetics of AQCH tablets would assist in further dose optimization with defined pharmacokinetic-pharmacodynamic relationship.