Pharmacokinetic modeling of single dose Kratom (mitragynine) in rats

Abstract

Event Abstract Back to Event Pharmacokinetic modeling of single dose Kratom (mitragynine) in rats Yuvenesan Jagabalan1, Hadzliana Zainal1*, Ammar Imad Hazim Al Ganaby2, Vikneswaran Murugaiyah1 and Surash Ramanathan2 1 School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia 2 Center for drug research, University of Science, Malaysia, Malaysia Background Mitragynine the principal alkaloid of M. speciosa leaf has been reported to be responsible for most of its pharmacological effects. Earlier studies have reported the pharmacokinetic properties of mitragynine (MG) following single oral dose administration. However, the selection of MG doses employed in these studies was derived empirically without proper scientific basis. In view of this, the present study was undertaken to determine MG dose-proportionality properties after repeated oral administration in rats. Methods In this study, eighteen rats were randomly assigned into three experimental groups (n = 6, each). The first group rats were orally treated with a single dose of 20 mg/kg MG. The second group was given a single oral dose of 40 mg/kg MG whereas the third group of rats received the 80 mg/kg MG dose orally. Blood was collected from the tail vein before the dosing and thereafter at specific time-points after drug administration. Blood samples were centrifuged and separated plasma samples were frozen prior to analysis using HPLC. Results The pharmacokinetics was best described by two-compartment distribution models with first order absorption. Estimated typical clearance (CL/F) value was 2.21 L.h-1 , absorption rate (Ka) of of 0.82 h-1 and volume of distribution (Vd) of 30.8 L. The stability of the model and predicted performance were confirmed by bootstrap method and numerical predictive check. Conclusion Based on the single dosing experimental rat data, the model provides a useful tool to quantify the pharmacokinetic parameters to propose an optimal dosing regimen in rats. Subsequently, the pharmacokinetic parameter can be modeled to the pharmacodynamics of MG for extrapolation into human use. Keywords: mitragynine, single dosing study, Two-compartment, Pharmacodynamic (PD), pharmacokinetic Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Miscellaneous Citation: Jagabalan Y, Zainal H, Al Ganaby A, Murugaiyah V and Ramanathan S (2019). Pharmacokinetic modeling of single dose Kratom (mitragynine) in rats. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00087 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: PhD. Hadzliana Zainal, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, 11700, Malaysia, hadz@usm.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan Google Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan Google Scholar Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan PubMed Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.