Pharmacokinetics And Tissues Distribution Of Curcumae Fat Emulsion In Beagle Dogs And Wistar Rats

OBJECTIVES:To develop a high performance liquid chromatography (HPLC) coupled with tandem mass spectrometry quantitative detection method for the determination of curcumol in animal plasma and tissues, and to evaluate its pharmacokinetics characteristics in Beagle dogs and the tissues distribution in Wistar rats.METHODS:1. Nign healthy Beagle dogs were divided into three groups. An liquor of blood were drawn at shaduled time before or 5, 10, 20, 30, 45min, 1.0, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0 and 5.0 hours after single iv administration of 7.5mg·kg^-1, 10mg·kgv, 12.5 mg·kg^-1 Curcumae Fat Emulsion, respectively, and the concentrations of curcumol in plasma were determined with HPLC-MS/MS method.The pharmacokinetic parameters of curcumol were calculated and evaluated with DAS software.2. Thirty healthy Wistar rats were divided into six groups. The heart, liver, brain, kidney and lung tissues were removed after 10mg·kg^-1 curcumae fat emulsion were injected through caudal vein at prescheduled time points the curcumol in tissues were determined with HPLC-MS/MS method, and the characteristics of its tissue distribution were evaluated.RESULTS:1. The pharmacokinetics parameters of curcumol after 7.5mg·kg^-1,10mg·kg^-1, 12.5 mg·kg^-1 Curcumae Fat Emulsion in Beogle dogs were as follows: t_1/2 (2.017±0.441), (1.741±0.166) and (2.306±0.755)h, AUC_0-5 , (13.926±3.129),(17.236±1.924) and (26.816±3.193) ng·mr^-1·h, AUC_0-∞, 15.073±2.722, 18.284±1. 998 and 29.571±3. 952 ng·ml^-1·h, C_max,24.9±5. 28, 37. 5±6. 81 and 56. 2±14. 2ng·ml^-1; MRT,0.891±0. 108, 0. 787±0.196 and 0. 838±0.082h; CL, 21.9±4.0, 24.9±6.0 and 18.4±1.2L·h^-1kg; Vd, 65.4±26.5, 62.0±13.4 and 61.2±19.8L·kg^-1, respectively.2. The curcumol distributions in heart, liver, brain, kidney and lung tissues 10min, 30min, 1h, 2h, 3h, 5h after 10mg·kg^-1 Curcumae Fat Emulsion through caudal vein were as follows, 10min,82.959±38. 055, 108. 848±65. 910, 10. 009±2. 970, 105. 187±42. 924 and 92. 379±17. 673ng·ml^-1; 30min, 21.022±12. 360, 32.663±40.209, 3.990±1.247, 40.661±18. 317 and 35. 317±6. 988ng·ml^-1; 1h, 16.202±19. 990, 23.013±19.536, 1.655±0.300, 26. 348±16. 108 and 18. 848±10. 424ng·ml^-1, 2h, 2.653±1. 764, 10.808±4.160, 1.560±0.388, 12. 759±9. 707 and 4. 764±2. 335ng·ml^-1; 3h, 2.252±0. 681, 9.406±7.882, 0. 726±0. 485, 7. 259±5. 386 and 3. 310±2. 059ng·ml^-1;5h,(not detectable),5.095±3. 019, 0.818±0.200, 4.738±4.053 and 2. 611±1. 323ng·ml^-1.CONCLUSIONS:1. It can be concluded that the disposition of curcumol in Beogle dogs after Cureumae Fat Emulsion were fitted with three-compartment model. AUC and Cmax were dose dependent, but not t_1/2.2. The curcumol was rapidly distributed into tissues from plasma in terms of highly selective affinity to liver and kidney.3. The developed method was rapid, highly sensitive and specific and could be used in curcumol pharmacokinetic studies in vivo.