Planta Med 2019; 85(04): 340-346
DOI: 10.1055/a-0770-3683
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Comparative Pharmacokinetics of Mitragynine after Oral Administration of Mitragyna speciosa (Kratom) Leaf Extracts in Rats

Bonnie A. Avery
1  Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA (present affiliation)
2  Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Sai P. Boddu
2  Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Abhisheak Sharma
1  Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA (present affiliation)
2  Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Edward B. Furr
3  Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
,
Francisco Leon
3  Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
4  Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA (present affiliation)
,
Stephen J. Cutler
3  Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
5  College of Pharmacy, University of South Carolina, Columbia, SC, USA (present affiliation)
,
Christopher R. McCurdy
3  Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA
4  Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA (present affiliation)
› Author Affiliations
Further Information

Publication History

received 24 July 2018
revised 09 October 2018

accepted 18 October 2018

Publication Date:
16 November 2018 (eFirst)

Abstract

Kratom (Mitragyna speciosa) has been examined for its opioid activity, especially for the treatment of opioid withdrawal and pain. Mitragynine, the most abundant alkaloid in kratom, is thought to be the major psychoactive alkaloid. An HPLC method was developed for the quantification of mitragynine in kratom leaf extracts. In addition, a multiple reaction mode based UPLC-MS/MS method was developed and validated for the quantification of mitragynine in rat plasma. Pharmacokinetic studies were performed by comparing a single intravenous dose of mitragynine (5 mg/kg, mitragynine hydrochloride) to a single oral dose of mitragynine (20 mg/kg, mitragynine hydrochloride), lyophilized kratom tea, and the organic fraction of the lyophilized kratom tea at an equivalent mitragynine dose of 20 mg/kg in rats. After intravenous administration, mitragynine exhibited a biexponential decrease in the concentration-time profile, indicating the fast distribution of mitragynine from the systemic circulation or central compartment to the peripheral compartments. Mitragynine hydrochloride, lyophilized kratom tea, and the lyophilized kratom tea organic fraction were dosed orally and the absolute oral bioavailability of mitragynine in rats was found to be 1.5- and 1.8-fold higher than that of mitragynine dosed alone. The results provide evidence that an equivalent oral dose of the traditional preparation (lyophilized kratom tea) and formulated/manufactured products (organic fraction) of kratom leaves provide better systemic exposure of mitragynine than that of mitragynine dosed alone.

Supporting Information