Pharmacokinetics Study of Realgar and Its Tissue Distribution in Rats after Single Dose and Multiple Dose of Oral Administration
- VernacularTitle:雄黄单次和多次给药在大鼠体内的药物动力学和组织分布
- Author:
Yishan TANG
;
Weiping OU
;
Ningsheng WANG
;
Qide LIU
;
- Publication Type:Journal Article
- Keywords:
Realgar;
Aarsenic;
Pharmacokinetics;
Tissue distribution;
Microwave digestion-atomic spectrophotofluorimetry;
Rats
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2000;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the pharmacokinetics of arsenic from Realgar in rats and tissue distribution after single dose and multiple dose of oral administration.Methods Rats were orally administrated with single dose(75 mg?kg~(-1)) and multiple dose (75 mg?kg~(-1)?d~(-1),one dose per day,15 continuous days) of Realgar respectively.Arsenic concen- trations in serum and arsenic contents in organs and tissues were determined by atomic spectrophotofluorimetry alter mi- crowave digestion pretreatment.PK Solutions 2.0~(TM) software was used to process experimental data.Results Half-life of absorption,distribution and elimination of arsenic in rat serum were 4.30,12.59 and 22.70 hours respectively after single dose administration.Arsenic concentration reached to maximum concentration (46.0?g?L~(-1)) at 3 hours after ad- ministration,and then decreased.Twelve hours after administration arsenic concentration increased to the second peak concentration (42.0?g?L~(-1)).When Realgar was orally administrated in a fixed close and at a fixed interval,arsenic concentration maintained a steady state from the 7th day after the first administration,and the half-life of elimination was 43.61 h.Arsenic could be detected in the main organs and tissues of rats after administration of a single dose.The ar- senic was most accumulated in the spleen,hair,lung and suprarenal gland organs,and kidney,heart,liver,bladder and skin came next.Brain,testis,muscle and tibia had the least amount of arsenic.After 15 continuous days of admin- istration,arsenic contents in kidney and bladder tissues increased appreciably besides suprarenal gland,lung,hair and spleen.After 2 weeks of discontinuation,arsenic contents in organs and tissues decreased by 21.1%～69.5 % except for heart.Conclusion Small amount of soluble arsenic in Realgar was absorbed in blood circulation.Absorption,distri- bution and elimination of arsenic from Realgar proceed slowly in rats after single dose of oral administration.Multiple dose of oral administration prolongs the elimination of arsenic.Arsenic distributes widely in rats organs and tissues.It is the first reported that high arsenic accumulation is found in the suprarenal gland,indicating that the suprarenal gland is prob- ably one of the target organs of Realgar.
