Pharmacokinetics of α‐mangostin in rats after intravenous and oral application

SCOPE: The xanthone α-mangostin is one of the major bioactive secondary metabolites in Garcinia mangostana. Until now, in vivo studies on the absorption, bioavailability, disposition, and metabolism of α-mangostin are limited. METHODS AND RESULTS: In the present study, an LC-MS/MS assay has been established for the determination of α-mangostin in rat plasma. The validated method was used successfully to support pharmacokinetic studies in rats after intravenous (i.v.) and oral administration. Both non-compartmental and compartmental analyses were performed, where the two-compartment body model had a good fit with the i.v. data. Following i.v. administration, the disposition of α-mangostin in rat plasma was biphasic, subdivided into a fast distribution and a slow elimination phase. The half-life of the distribution phase was 3 min, and that of the terminal elimination phase 3.5 h, indicating a high tissue binding. However, for oral administration, the bioavailability was so low that it was not possible to obtain a full concentration-time profile. CONCLUSION: Although pure α-mangostin has shown a variety of pharmacological activities in in vitro assays at present it is uncertain if the same magnitude of effects will be achieved in vivo when its low bioavailability is considered.