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

Avery, Bonnie A.; Boddu, Sai P.; Sharma, Abhisheak; Furr, Edward B.; León, Francisco; Cutler, Stephen J.; McCurdy, Christopher R.

doi:10.1055/a-0770-3683

Cited by 37 publications

(50 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The alkaloidal fraction, ethanolic extract, and lyophilized tea were prepared in‐house from authenticated kratom plant leaves and analyzed for alkaloid content. The results of the analysis indicated that the alkaloidal fraction, ethanolic extract, and lyophilized tea contained 33.6, 6.2, and 0.7% of mitragynine, which is less than the mitragynine content reported in earlier publications . There is a possibility that earlier reported studies did not separate the four mitragynine diastereomers, resulting in over‐quantification of mitragynine in these methods.…”

Section: Resultsmentioning

confidence: 72%

“…It is necessary to separate alkaloids sharing the same ion transitions chromatographically to assure their peak purity; otherwise, samples may be inappropriately over quantified for certain alkaloids. For example, mitragynine might have been over quantified along with its three other co‐eluting diastereomers by earlier reported isocratic or short gradient methods . Therefore, various mobile phase compositions (mobile phase A: aqueous ammonium acetate, water containing acetic acid, aqueous ammonium formate, or water containing formic acid; pH 3.0–6.8, mobile phase B: acetonitrile and methanol) and columns (Acquity UPLC BEH C18, CSH C18, Cyano, and HILIC) were tested to achieve at least a resolution of ≥2 between alkaloids sharing the same ion transitions with Gaussian peak shapes.…”

Section: Resultsmentioning

confidence: 99%

“…The ethanol portions were combined and dried under reduced pressure to obtain an ethanolic extract. The method described by Avery et al was implemented for aqueous extraction (tea) . Dry leaves of Mitragyna speciosa (200 g) were placed in a Fernbach conical flask with 2 L of water and boiled for 20 minutes, the sample was filtered and the filtrate was dehydrated using a lyophilizer (Labconco ® 2.5 L free zone) to yield lyophilized kratom tea.…”

Section: Methodsmentioning

confidence: 99%

“…A recent study reported that the phytochemicals present in both the organic fraction and lyophilized tea of kratom are able to affect the pharmacokinetics of mitragynine. The observed oral bioavailability of mitragynine was higher in rats dosed with the organic fraction or lyophilized tea, than in those dosed with mitragynine alone . Based on the traditional use of kratom for centuries and the available literature, kratom could be considered a potential treatment for opioid withdrawal and pain, but this may be anecdotal.…”

Section: Introductionmentioning

confidence: 99%

“…The observed oral bioavailability of mitragynine was higher in rats dosed with the organic fraction or lyophilized tea, than in those dosed with mitragynine alone. 21 Based on the traditional use of kratom for centuries and the available literature, kratom could be considered a potential treatment for opioid withdrawal and pain, 1 but this may be anecdotal.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra‐performance liquid chromatography−tandem mass spectrometry

Sharma

Kamble

León

et al. 2019

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self‐treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra‐performance liquid chromatography−tandem mass spectrometry (UPLC−MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7‐hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1–200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid‐rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%–38.7% w/w), paynantheine (0.3%–12.8% w/w), speciociliatine (0.4%–12.3% w/w), and speciogynine (0.1%–5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7‐hydroxymitragynine, isocorynantheidine) were also quantified (0.01%–2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.

show abstract

Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra‐performance liquid chromatography−tandem mass spectrometry

Sharma

Kamble

León

et al. 2019

Drug Testing and Analysis

Self Cite

View full text Add to dashboard Cite

show abstract

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Henningfield

Rodricks

Magnuson³

et al. 2022

Psychopharmacology

View full text Add to dashboard Cite

Rationale Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway. Objectives Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188–197, 2020). Methods Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride. Findings Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related. Conclusions Consistent with mitragynine’s pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.

show abstract

Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities

Alsarraf

Myers

Culbreth

et al. 2019

Curr Emerg Hosp Med Rep

View full text Add to dashboard Cite

Purpose of Review This review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal. Recent Findings Multiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events. Summary Reports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.

show abstract

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

Cited by 37 publications

References 27 publications

Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra‐performance liquid chromatography−tandem mass spectrometry

Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra‐performance liquid chromatography−tandem mass spectrometry

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities

Contact Info

Product

Resources

About