ABSTRACT
BACKGROUND: In order to improve the medication safety and remove export obstacles of Chinese preparations contained heavy metal and arsenide (cinnabar, realgar), it is necessary to carry on the evaluation on the efficacy and safety of cinnabar and realgar. At present, it has not been clear concerning to the pharmacodynamic mechanism of cinnabar and realgar in compound prescriptions yet.OBJECTIVE: To study the differences in cinnabar and realgar in angong niuhuang wan in the organism physiologically and pathologically so as to probe into those pharmacodynamic mechanism.DESIGN: A randomized and controlled trial.SETTING: Institute of Clinical Pharmacology of one university.MATERIALS: The experiment was performed in Institute of Clinical Pharmacology of Guangzhou University of Traditional Chinese Medicine in January 2003. Totally 51 male SD rats weighted varied from 250 g to 300 g were employed, provided by Experimental Animal Center of First Military Medical University of Chinese PLA.METHODS: SD rats were randomized into 6 groups(8-10 rats/group),named as normal group, normal & angong niuhuang san (integral recipe) group(278 mg/kg), normal & cinnabar and realgar omitted angong niuhuang san(disassembled recipe) group(222.7 mg/kg), cerebral edema model group(ligature on unilateral carotid artery by injection of pertussis bacilli (PB), 2 500 million/kg), model & integral recipe group (medication 278 mg/kg was done 1 hour before model preparation), model & disassembled recipe group(medication 222.7 mg/kg was done 1 hour before model preparation) . Five hours later after once medication(4 hours later after PB injection in model group), blood was collected and brain homogenate was prepared.MAIN OUTCOME MEASURES: Brain tissues, serum lactate dehydrogenase(LDH) activity and percentage enzyme activity of lactate dehydrogenase isoenzymes (LDH1-5).RESULTS: Compared with normal group, the general activity of LDH in normal & integral recipe group and normal & disassembled recipe group was significantly improved by 32.4% to 38.4% ( P ＜ 0.05); percentage enzyme activity of LDH1,2 was significantly increased( P ＜ 0.01 ), and that of LDH4, 5 was reduced( P ＜0.01) . Except LDH5, there were no significant differences in enzyme activity of isoenzymes in two groups. Compared with model group, the general activity of LDH in model & integral recipe group and model & disassembled recipe group was significantly improved by 23.4% to 38.5% ( P ＜ 0.01); percentage enzyme activity of LDH5 was significantly increased( P ＜ 0.01 ), there were no significant differences in two groups. In model & integral recipe group, percentage enzyme activity of LDH2,3 was significantly decreased( P ＜ 0.01), and that of LDH1,4 was no significant change. In model & disassemble recipe group, percentage enzyme activity of LDH1,4 was significantly reduced( P ＜ 0. 05, 0.01 ) and that of LDH2,3 was no significant change.CONCLUSION: In normal physiological state, angong niuhuang san produces a certain injuries on cardiac muscle and kidney. In pathological state of infectious cerebral edema, both integral and disassembled recipes inhibit LDH enzymes that have been over-activated, but the significant differences did not presented between both. Cinnabar and realgar in compound prescript provide the effects in various degrees on levels of LDH isoemzymas.
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.
ABSTRACT
Objective To compare the pharmacokinetics of borneolum syntheticum(BS)and borneol in compound Danshen dropping pills in rats.Method Rats were administrated orally with BS or Danshen dropping pills containing equal amount of borneol in a single dose.The blood contents of borneol at a series of time points were assayed by GC-MS and GC-FID after administration.The drug-time curve was estimated by PK Solution 2.0 pharmacokinetic software(USA).Results The pharmacokinetic parameters are quite different between the single dose of BS and the borneol in the compound Danshen dropping pills:the velocity constants of absorption(2.630h-1),distribution(1.788 h-1)and elimination(0.273 h-1)of BS were much greater than those(1.635h-1,0.784h-1,0.116h-1)of the same quantity of borneol in compound Danshen dropping pills,while the Tmax(0.5 h)of former was shorter than that(0.75 h)in the latter,and the Cmax(16.8 ?g/mL)in the former was about half of the latter(31.02 ?g/mL).And,at the 18h after administration,the former blood concentration(0.043 ?g/mL)was approximately one tenth of the latter.Conclusion It is suggested that we should pay attention to the influence of other ingredients on the main objective component in the study of pharmacokinetics of compound traditional chinese drug.
ABSTRACT
The concentrations of borneol in the serum and brain tissue of rats were determined by gas chromatography. Using brain tissue as a relatively independent system, PHARMFIT and PCNONLIN softwares are applied for the kinetic analysis of the infracorporal process of borneol in order to find out and compare the pharmacokinetic characteristics of borneol in the brain and serum. The results showed that borneol was absorbed very rapidly in the gastrointestinal tract and readily permeates the blood-brain barrier into brain tissue. There was a higher specific value of borneol concentration in the brain and serum. Moreover, the half life of distribution phase of borneol in the brain was three times higher than that in the serum. But the constants of elimination rate of borneol in the brain and serum decreased simultaneously and parallelly, hence the accumulation of borneol in brain will not be found.