BackgroundKratom, known botanically as Mitragyna speciosa (Korth.), is an indigenous tree in Southeast Asia. Kratom is currently easily available worldwide via special shops and the Internet to use as a drug of abuse, opioid alternative, or pain killer. So far, the pharmacokinetics of this plant has been studied only in animals, and there is no such study in humans. The major abundant active alkaloid in Kratom, mitragynine, is one of the promising new chemical substances to be developed as a new drug. The aim of this study was to examine the pharmacokinetics of mitragynine and assess the linearity in pharmacokinetics in chronic users.MethodsSince Kratom is illegal in Thailand, studies in healthy subjects would be unethical. We therefore conducted a prospective study by enrolling ten chronic, regular, healthy users. We adjusted the steady state in each subject by giving a known amount of Kratom tea for 7 days before commencement of the experiment. We admitted and gave different oral doses to subjects to confirm linearity in pharmacokinetics. The mitragynine blood concentrations at 17 times points and the urine concentrations during the 24-hour period were collected and measured by liquid chromatography-tandem mass spectrometry method.ResultsTen male subjects completed the study without adverse reactions. The median duration of abuse was 1.75 years. We analyzed one subject separately due to the abnormal behavior of blood concentration. From data of nine subjects, the pharmacokinetic parameters established were time to reach the maximum plasma concentration (0.83±0.35 hour), terminal half-life (23.24±16.07 hours), and the apparent volume of distribution (38.04±24.32 L/kg). The urine excretion of unchanged form was 0.14%. The pharmacokinetics were observed to be oral two-compartment model.ConclusionThis was the first pharmacokinetic study in humans, which demonstrated linearity and was consistent with the oral two-compartment model with a terminal half-life of about 1 day. The pharmacokinetic linearity and parameters reported are necessary pharmacological information of Kratom, and there is a possibility for it to be developed medically as a pain killer or better opioid substitute in the future.

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Human xylazine poisoning is uncommon. This report describes the use of xylazine for intentional poisoning with criminal intent. Two incidents occurred within 3 weeks: the first involved one victim, and the second involved two victims. The clinical presentations were brief coma, bradycardia, hypotension, and hyperglycemia. The victims recalled having been given a drink from a stranger in a hospital waiting room before loss of consciousness. In the first case, general drug screening by gas chromatography/mass spectrometry (MS) revealed xylazine in the gastric contents, but liquid chromatography-tandem MS (LC-MS/MS) of serum did not. In the second incident, LC-MS/MS screening of both victims' urine and serum samples revealed an unknown peak in the total ion chromatograms, which a molecular mass database identified as morantel or xylazine. The latter was confirmed by comparison with a xylazine standard. Based on this report, we suggest that xylazine should be classified as a controlled drug.