Pharmacokinetic Study of Rhein and its Carboxyl-esterification Derivatives in Rats

AimTo explore the effects of carboxyl-esterification on pharmacokinetics of rhein in rat.MethodsRhein methylate (REM) and Rhein ethylate (REE) were used as model drugs while rhein (RE) as a positive control. The simultaneous detection of three analytes in rat plasma samples was carried out by an HPLC-fluorescence method. Single dose of RE, REM or REE was administered to rats by both ig route at 70 mg·kg−1 and iv route at 0.7 mg·kg−1.ResultsREM and REE were entirely metabolized to rhein after ig and iv administration of either REE or REM to rats and only rhein was detected in plasma. Therefore, the pharmacokinetic comparisons among RE, REE and REM in rat were carried out based on the profiles of rhein in rat plasma after the administration of each compound. The main pharmacokinetic parameters of REM, REE and RE after ig administration were as follows: cmax (0.058 ± 0.035), (0.95 ± 0.090), (42.66 ± 14.41) mg·L−1; Tmax (6.7 ± 2.3), (10.7 ± 2.3), (0.9 ± 0.1) h; t1/2β (6.0 ± 1.7), (6.4 ± 1.0), (3.2 ± 0.6) h; AUC0-∞ (1.03 ± 0.76), (12.79 ± 0.96), (80.28 ± 13.59) h·mg·L−1.ConclusionThe reconstruction of carboxyl-esterification can significantly reduce the net exposure amount of rhein in vivo, leading to its inaptitude in the development of drug precursors of rhein.