2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows\nexcellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to\nbe evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify\ntHGA in rat plasma. The method showed good linearity (0.5â??80 ng/mL). The accuracy and precision\nwere within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first\ntwo groups were given oral administrations of unformulated and liposome-encapsulated tHGA,\nrespectively, while the third group received intraperitoneal administration of liposome-encapsulated\ntHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life\n(t1/2) and area under curve (AUC0â??24) values for intraperitoneal administration were 54.6 ng/mL,\n1.5 h, 6.7 h, and 193.9 ng/mL-h, respectively. For the oral administration of unformulated and\nformulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values\nwere 6.9 and 6.6 h, and AUC0â??24 values were 17.6 and 40.7 ng/mL-h, respectively. The liposomal\nformulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a\n2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized.\nThe metabolites were mainly products of oxidation and glucuronide conjugation.
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