Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal micron Liuhe Pill ointment in rats.

Objective: To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill, MLHP) components in anesthetized rats.
Methods: Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry.
Results: Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2α of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P<0.05), while there was no difference for T1/2α of aloe emodin. The peak concentration and area under curve of all three components were much higher in the AP group than those in the normal group with MLHP in external application for 48 h (P<0.05). Furthermore, the mean residence time (MRT) and maximum plasma concentration (Tmax) of emodin and aloe emodin were obviously longer in the AP model group than those in the normal control group (P<0.05). There was no significant difference for Ka of all components between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in the AP model group than in the normal group (0.61±0.54 ng/mL, 0.42±0.37 ng/mL, respectively,P<0.05). Aloe emodin could be detected in all rats' pancreas at 48 h in both groups and their mean pancreatic concentration were similar (0.31±0.24 ng/mL, 0.33±0.17 ng/mL, respectively,P>0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group.
Conclusion: AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats.