Abstract
Increasing use of the botanical kratom to self-manage opioid withdrawal and pain has led to increased kratom-linked overdose deaths. Despite these serious safety concerns, rigorous fundamental pharmacokinetic knowledge of kratom in humans remains lacking. We assessed the pharmacokinetics of a single low dose (2 g) of a well-characterized kratom product administered orally to six healthy participants. Median concentration-time profiles for the kratom alkaloids examined were best described by a two-compartment model with central elimination. Pronounced pharmacokinetic differences between alkaloids with the 3S configuration (mitragynine, speciogynine, paynantheine) and alkaloids with the 3R configuration (mitraciliatine, speciociliatine, isopaynantheine) were attributed to differences in apparent intercompartmental distribution clearance, volumes of distribution, and clearance. Based on noncompartmental analysis of individual concentration-time profiles, the 3S alkaloids exhibited a shorter median time to maximum concentration (1–2 vs. 2.5–4.5 h), lower area under the plasma concentration-time curve (430–490 vs. 794–5120 nM × h), longer terminal half-life (24–45 vs. ~12–18 h), and higher apparent volume of distribution during the terminal phase (960–12,700 vs. ~46–130 L) compared to the 3R alkaloids. Follow-up mechanistic in vitro studies suggested differential hepatic/intestinal metabolism, plasma protein binding, blood-to-plasma partitioning, and/or distribution coefficients may explain the pharmacokinetic differences between the two alkaloid types. This first comprehensive pharmacokinetic characterization of kratom alkaloids in humans provides the foundation for further research to establish safety and effectiveness of this emerging botanical product.
Highlights
The United States was the leading consumer of opioids worldwide between 1990 and2016 [1]
Hospitalizations and deaths due to opioid overdose have increased exponenti during the last four decades, with the most recent cases attributed to ultrapotent licit illicit fentanyl products [2]
According to a report from the Centers for Disease Con and Prevention, approximately 48,000 people died of opioid overdose in2 of opioid users are increasingly seeking safer alternatives to pharmaceut drugs
Summary
The United States was the leading consumer of opioids worldwide between 1990 and2016 [1]. Hospitalizations and deaths due to opioid overdose have increased exponentially during the last four decades, with the most recent cases attributed to ultrapotent licit and Pharmaceutics 2022, 14, 620. The United States was the leading consumer of opioids worldwide between 1990. Hospitalizations and deaths due to opioid overdose have increased exponenti during the last four decades, with the most recent cases attributed to ultrapotent licit illicit fentanyl products [2]. According to a report from the Centers for Disease Con and Prevention, approximately 48,000 people died of opioid overdose in of 16 alone. Opioid users are increasingly seeking safer alternatives to pharmaceut drugs. According a report the Centers for Disease Control (Korth.) and.
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