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. 2022 May;8(5):e09416.
doi: 10.1016/j.heliyon.2022.e09416. Epub 2022 May 13.

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

Sajad Khaliq Dar  1 , Sudershan Kumar  1 , Sovan Maiti  1 , Shilpi Dhawan  1 , Sadhna Joglekar  1 , Upasana Arora  1 , Rinku Kalra  1 , Sumit Madan  1 , Altaf A Lal  1 , Venugopal Singamaneni  2 , Prasoon Gupta  2 , Utpal Nandi  2 , Deepika Singh  2 , Arshad H Khuroo  1
Affiliations

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

Sajad Khaliq Dar et al. Heliyon. 2022 May.

Abstract

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 Cocculus hirsutus (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 (Cmax) 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.

Keywords: LC-MS/MS; Phoenix; SAS; Simulation; Sinococuline; Steady state; Tolerability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Linear Plot of mean plasma concentration of Sinococuline Day 1 & Day 10 following multiple ascending oral dose of AQCH tablet in healthy adult human subjects under fasting condition [Cohort I (100 mg), II (200 mg), III (400 mg), IV (600 mg) & V (800 mg)].
Figure 2
Figure 2
Linear Plot of mean trough concentration (Ctrough) of Sinococuline.
Figure 3
Figure 3
Linearity plot of Sinococuline of Cmax and AUC0-8 on Days 01 and 10.
Figure 4
Figure 4
Simulation model showing the predicted data (Solid line) vs observed data (Circle).
Figure 5
Figure 5
The predicted profile at 200(1X), 400(2X), 600(3X) and 800 (4X) mg doses for days 01–10 using simulation model.
See this image and copyright information in PMC

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