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Purpose   To study the pharmacokinetics of the 6 alkaloids (aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine) in raw Aconiti Kusnezoffii Radix ( Caowu ) (RC) and Chebulae Fructus- ( Hezi -) processed  Caowu  (HC) in the rats being, respectively, administrated with RC and HC in the dosage forms of powder and decoction and to demonstrate the mechanism of detoxification of HC.Methods   The rats were randomly divided into 4 groups and, respectively, given RC powder, HC powder, RC decoction, and HC decoction by intragastric administration. The contents of the 6 alkaloids in the plasma of the rats were detected at different time points by the UPLC-MS/MS method, and DAS 3.2.7 software was used to calculate, compare, and analyze the detected pharmacokinetic parameters.Results   Compared with those of the RC powder, the values of AUC 0‐ t   and  C  max  of the HC powder were all reduced, whereas the values of  t  1/2 z   and  T  max  were mostly increased. Compared with those of the RC powder, the values of AUC 0‐ t  ,  C  max , and  t  1/2 z   of the RC decoction were decreased and the value of  T  max  of the RC decoction was increased. Compared with those of the RC decoction, the values of AUC 0‐ t  ,  t  1/2 z  , and  C  max  of the diester diterpenoid alkaloids of the HC decoction were all increased. However, there was no marked difference between the pharmacokinetic parameters of the HC powder and the HC decoction.Conclusions   A decrease in the level of absorption and in the rate of elimination of the alkaloids can be detected when HC is administrated in the dosage form of the powder, explaining that in traditional Mongolian medicine (TMM), the purpose of using HC in the dosage forms of pills and powder is for decreasing the toxicity and prolonging the efficacy duration of HC. Decocting can greatly decrease the plasma concentration of the diester diterpenoid alkaloids in RC and increase their rate of elimination. The influence of decocting on RC is greater than that on HC, explaining the rationality of the steaming and boiling methods for processing  Caowu  and the rationality of boiling  Caowu  for a longer time beforehand in preparing an herb decoction containing  Caowu  in TCM.

biomed research international

Influence of Different Dosage Forms on Pharmacokinetics of 6 Alkaloids in Raw Aconiti Kusnezoffii Radix (Caowu) and Chebulae Fructus- (Hezi-) Processed Caowu by UPLC-MS/MS