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Hepatic drug transporters(HDTs),including uptake transporters and efflux transporters, play an important role in drug distribution and elimination in the liver. The influx HDTs include organic anion transporters,organic cation transporters,organic anion transporter polypeptides and Na+-tauro-cholate cotransporting polypeptide. The efflux HDTs include multidrug resistance proteins,multidrug resistance-associated proteins,breast cancer resistance protein and bile salt export pumps. Major research methods involve gene knock-out animals,isolated perfused livers,liver slices,primary hepato-cytes and transfection cells. They have been used in study of drug distribution,drug-drug interaction and drug toxicity.
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Physiologically based pharmacokinetic model (PBPK), a mechanistic mathematic model, which can simulate the absorption, distribution, metabolism and excretion of drugs, is being more widely used in pharmaceutical research and development areas. This article reviews primarily the recent advances in the procedure of establishing a PBPK model, including specifying of the PBPK model structure, specification of the tissue model, writing of equations, set of model parameters, simulation and evaluation. Application significance, major challenges and future developments of PBPK model in pharmaceutical areas are also discussed.
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Mammal multidrug and toxin extrusion proteins (MATEs) play an important role in the transport of organic cations in the body. MATEs mediate the final excretion step for multiple organic cation drug used clinically and important endogenous substances. This article reviews the discovery, type, gene coding and polymorphism, body distribution, classification of substrates and inhibitors and their research method of MATEs. The article also discusses the major research significance of MATEs with examples.
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Objective To discuss the diagnostic value of color Doppler echocardiography in small coronary-to-pulmonary fistula (SCPF) in children. Methods The clinical data of children who were diagnosed CPF by color Doppler echocardiography during 2011-2012 in my hospital were analyzed retrospectively. Results Seventeen cases with CAF including one diagnosed by forensic report and 8 cases diagnosed by AGA. Conclusion The results indicated that SCPF detection rate could be improved largely by observing spraying-up sign experienced in pulmonary artery diastolic combined with rich flow signal of coronary in color Doppler. In addition, it is valuable to diagnose children's SCPF by color Doppler echocardiography.
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In this paper, absorption and pharmacokinetic study of Radix Rehmanniae was studied by liquid chromatography coupled with mass spectrometry method after oral administration to rats. By comparing the chromatograms of ultraviolet, full scan, extracted ion and selective reaction monitoring (SRM) of standard solution, Radix Rehmanniae, blank plasma and rat plasma post drug administration, catalpol and ajugol were found to be the main compounds absorbed from Radix Rehmanniae. Plasma concentrations of aucubin, dihydrocatalpol, rehmannioside A (or rehmannioside B/ melittoside) and rehmannioside D were very low. Quantitative method for catalpol and aucubin and semi-quantitative method for other compounds in rat plasma were established. The pharmacokinetic study of those absorbed components was conducted after oral administration of 6 g x kg(-1) Radix Rehmanniae water extract to rats. Cmax, t(1/2) and AUC(0-infinity) of catalpol and ajugol were (2349.05 +/- 1438.34) and (104.25 +/- 82.05) ng x mL(-1), (0.86 +/- 0.32) and (0.96 +/- 0.37) h, (4407.58 +/- 2734.89) and (226.66 +/- 188.38) ng x h x mL(-1), respectively. tmax was at 1.00 h for catalpol and ajugol. Both catalpol and ajugol were absorbed and excreted rapidly.
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To study the effect of Banxiaxiexin Tang and different conbinations on CYP450 in rat liver microsomes, from the point of liver metabolism, evaluate significance of Banxiaxiexin Tang compatibility. The rats were randomly divided into five groups: Banxiaxiexin Tang group, pungent-swelling group, bitter-descending group, sweet-invigorating group and control group, which were all given decoction by gavage. Using liver microsomes in vitro incubation method, probe substrate were incubated and their metabolites was detected by ultra-high performance liquid chromatography, then was calculated metabolic rate to reflect the drug-treated liver microsomes CYP2C6, CYP2E1, CYP3A1/2 activity. The results showed that comparing with the control group, both Banxiaxiexin Tang group and bitter-descending group showed inhibition on all enzyme subtype (P < 0.01), pungent-swelling group showed significant inhibition on CYP2C6, but no inhibition on CYP2E1 and CYP3A1/2; sweet-invigorating group showed inhibition on CYP2C6 and CYP2E1, but no inhibition on CYP3A1/2. Compared the inhibition on CYP with the three conbinations, bitter-descending group was significant higher than other groups. Banxiaxiexin Tang group showed inhibition on rat liver microsomes CYP450, and the activity maybe come from bitter-descending group.
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Animals , Male , Rats , Cytochrome P-450 Enzyme System , Metabolism , Drug Compounding , Liver , Plant Extracts , Pharmacology , Rats, Sprague-DawleyABSTRACT
A sensitive and reliable liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) method was established to simultaneously quantitate four categories of compounds (isoflavonoids, flavonoids, alkaloids and saponins) in Gegen-Qinlian decoction (GQD). These compounds were separated by a Shiseido CAPCELL PAK C18 column with a linear gradient consisting of 0.1% (v/v) formic acid in water (A) and 0.1% (v/v) formic acid in acetonitrile (B), and delivered at a flow rate of 0.3 mL/min. All the analytes were determined by electrospray positive ionization tandem mass spectrometry in a multiple reaction monitoring (MRM) mode. Linearity, accuracy, precision, recovery and stability of the method were evaluated with the validation over the range of 4.0-538 5 ng/mL. The proposed method was applied to the analysis of a Chinese herbal preparation GQD successfully.
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The pharmacokinetic process of traditional Chinese medicine remedies are mainly studied by measuring the time course of either biological responses or active component concentration. In recent years, some progress has been achieved in developing new methods. This review article outlined the rationale and characteristics of these methods and evaluated their advantages and disadvantages when applied in study of traditional Chinese medicine remedy. Some future research directions in the field were prospected.
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Aim To study pharmacokinetics and bioavailablity of domestic penicillin V dispersion tablet in healthy volunteers. Methods According to the crossover design, each volunteer in two groups was orally given a single dose ( 0.75 g ) of domestic penicillin V dispersion tablet or imported penicillinV tablet alternately and the plasma concentrations were determined by RP HPLC. The pharmacokinetic parameters were obtained by using ATPK program and calculated on the basis of open single compartment model. Results After a single oral dose( 0.75 g ), the t 1/2(ke) was ( 0.75 ? 0.10 ) h and ( 0.70 ? 0.14 ) h ,the c max was( 8.44 ? 2.40 ) mg?L -1 and ( 8.75 ? 3.04 ) mg?L -1 at ( 0.56 ? 0.11 ) h and ( 0.63 ? 0.17 ) h and AUC 0～4 was( 8.44 ? 2.40 ) mg?h?L -1 and ( 8.75 ? 3.04 ) mg?h?L -1 for two formulations, respectively. Relative bioavailability of domestic penicillin V dispersion tablet was ( 90.50 ? 8.84 )%. Conclusion The result shows that the two formulations are bioequivalent.
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Objective To investigate the effect of Xiexin Decoction(XXD) on the early diabetic nephropathy(DN) of diabetic rats induced by high-fat diet with injection of streptozotocin(STZ).MethodsMale Sprague-Dawley rats were divided into two groups and fed with normal pellet diet(NPD) or high-fat diet(HFD),respectively,for a period of four weeks and then HFD-fed rats were ip injected with STZ.The diabetic rats were divided into three groups: model group,XXD group,and metformin group.After 13-weeks ig administration,fasting blood glucose(FBG),glycated hemoglobin(HbAlc),blood lipids(TG and TC),serum insulin(INS),renal function,kidney index,albumin in urine,and the renal histology and ultrastructure were observed.Results Compared with the model group,XXD reduced the levels of water intake,food consumption,urine volume,HbAlc,insulin resistance index(IRI),creatinine clearance rate(CCr),albumin in urine and blood lipids(P
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objective To study the pharmacokinetics of lignans components in Shengmai granule in volunteers and in mice. Methods After oral administration of Shengmai granule (3.6 g/person) for the volunteers and ig administration of the drug (4.7 g/kg) for the mice, the plasma was collected at different time points. The lignans components in Shengmai granule and in the plasma were analyzed by HPLC to monitor the changes of plasma concentration of schisandrind. Pharmacokinetic parameters were calculated from the plasma concentration- time data with the 3P97 software package. Results After oral administration of Shengmai granule by volunteers and mice, schisandrin and some new components in plasma were detected. The new components may be the metabolites of schisandrin. The main pharmacokinetic parameters of schisandrin in mice and in volunteers were as follows: T1/2ka was 0.03 and 0.04 hour, T1/2ke 0.88 and 0.86 hour, Vd 19.12 and 1.73 L? kg- 1, CL 15.06 and 1.46 L? h- 1? kg- 1, Cmax 1.196 and 0.098 mg? L- 1, Tpeak0.21 and 0.50 h, AUC0- ∞ 1.096 and 0.137 mg? h? L- 1, respectively. Conclusion Schisandrin in Shengmai granule can be absorbed in the volunteers and mice after oral administration. It can be absorbed and eliminated rapidly, and can be transformed into the metabolite. The pharmacokinetics of plasma Schizandrin complies with linear kinetic course.
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AIM: To investigate the influence of Sijunzi Decoction(Radix et Rhizoma ginseng,Rhizoma atractylodis macrocephalae,poria,Radix et Rhizoma glycyrrhizae) on the pharmacokinetics of Levofloxacin(LVFX) in rats with deficiency of spleen. METHODS: Twenty-four rats were randomly divided into four groups: NS(normal rats given 0.9% saline solution),NS+SJZT(normal rats given 0.9% saline solution and Sijunzi Decoction),R(rats pretreated with Reserpine) and R+SJZT(rats pretreated with Reserpine and then cured with Sijunzi Decoction).After a single oral administration of LVFX 20 mg/kg,blood samples were collected at different intervals.The concentrations of LVFX plasma were determined by HPLC.Pharmacokinetic parameters were determined from the plasma concentration-time data. RESULTS: Reserpine led to the syndromes similar to the deficiency of spleen,a traditional Chinese medicine syndrome.The pharmacokinetic parameters of LVFX in NS,NS+SJZT,R and R+SJZT groups were as follows: AUC_((0-∞))=(8.55 ?0.99),(7.41?1.39),(4.68?0.95) and(7.89?1.41)mg/(L?h),respectively and C_(max)=(3.31?0.63),(2.38?1.15),(1.29?0.45) and(3.35?1.15) mg/L,respectively.Compared with the parameters of LVFX in NS group,Reserpine markedly decreased AUC_((0-∞)) and C_(max) of LVFX(P
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AIM:To study the urinary pharmacokinetics of five anthraquinones after oral administration of Xiexin Decoction(Radix et Rhizoma rhei,Rhizoma coptidis and Radix scutellariae) in rats.METHODS:A high-performance liquid chromatographic method with fluorescence detection(HPLC-FLD) was established and validated the quantification for five anthraquinones(aloe-emodin,rhein,emodin,chrysophanol and physcion) in rat urine.SD rats were given 12 g/kg of Xiexin Decoction.Urine was collected before and after perfusion.Anthraquinones components in urine were measured by HPLC-FLD.Urinary pharmacokinetic parameters were determined according to urinary output-time data.RESULTS:After oral administration of Xiexin Decoction all the five anthraquinones were excreted from the urine.The excretion T_ 1/2 of aloe-emodin,rhein,emodin,chrysophanol and physcion were 3.46?1.18,3.24?0.60,4.69?1.99,4.49?1.63,5.65?1.74 h,respectively.The amounts of aloe-emodin,rhein,emodin,chrysophanol and physcion excreted from urine during 0～48 h were(11.28?4.30)?g,(116.73?17.46)?g,(5.48?2.92)?g,(9.53?2.67)?g,(0.41?0.20)?g,respectively.CONCLUSION:After oral administration of Xiexin Decoction five anthraquinones were excreted from urine and a small quantity of five anthraquinones excreted from urine in rats is less than 10% of oral dose.
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AIM: To study the pharmacokinetics of flavonoids in mice after ig administration of Xiexin Decoction (Radix et Rhizoma rhei, Rhizoma coptidis, Radix Scutellariae). METHODS: Mice were given a single ig dose of Xiexin Decoction 4.5, 9.0 or 18.0 g/kg. Flavonoids in plasma were analysed by HPLC and plasma concentration of baibalin was determined. Pharmacokinetic parameters were calculated from the plasma concentration-time data with the DAS software package. RESULTS: After ig administration of Xiexin Decoction in mice, baicalin, baicalein and another flavonoid were detected in plasma and baicalin concentration was the highest of the three kinds of flavonoids in plasma. After a single ig dose of Xiexin Decoction 4.5, 9.0 or 18.0 g/kg, the pharmacokinetic parameters of baicalin were as follows:T_ 1/2 =2.77、5.69、6.20 h,AUC_ 0-∞ =9.09、23.49、39.57 ?g?h/mL,CL= 12.52 、 6.962 、 11.50 L?h/kg,V_d= 50.11 、 79.56 、 102.95 L/kg,C_ max1 =1.89、3.32、4.79 ?g/mL(T_ p1 = 0.08 h ), C_ max2 =1.46、2.57、4.16 ?g/mL(T_ p2 =3 h), respectively. CONCLUSION: Three kinds of flavonoids can be absorbed after ig administration of Xiexin Decoction in mice, of which baicalin is the major component.
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AIM: To determine the contents of protocatechuic acid,peoniflorin,coumarin,cinnamic acid,cinnamaldehyde and glycyrrhizic acid in categorized formulas about Guizhi Decoction (Ramulus cinnamoni,Radix paeoniae alba,Rhizoma zingiberis recens,Radix et Rhizoma glycyrrhizae and Fructus jujubae) by HPLC.METHODS: The gradient elution mode was applied in chromatographic separation.The C18 column was used with the mobile phase of 0.05% phosphoric acid-acetonitrile,flow rate was at 1.0 mL/min,detection wavelength at 230 nm and 254 nm,and the column temperature was at 30 ℃.The contents of the above-mentioned six constituents were determined in Guizhi Decoction,Guizhi Decoction plus Ramulus cinnamoni and Guizhi Decoction plus Radix paeoniae alba,respectively.The differences among all combinations were tested by one-way analysis of variance using SPSS software.RESULTS: The concentrations of the above-mentioned six constituents in different decoctions were simultaneously determined by HPLC and the linear equations of six constituents were established.Compared with Ramulus Cinnamomi alone,cinnamic acid content decreased and protocatechuic acid content increased in categorized formulas about Guizhi Decoctions significantly,but then coumarin content increased in Guizhi Decoction and Guizhi Decoction plus Radix paeoniae alba.Compared with Radix Paeoniae Alba alone,peoniflorin content decreased in categorized formulas about Guizhi Decoctions significantly.Compared with Radix et Rhizoma Glycyrrhiza alone,glycyrrhizic acid content increased in categorized formulas about Guizhi Decoctions significantly.CONCLUSION:The methods are accurate,reproducible and suitable for determineation of the contents of six constituents in categorized formulas about Guizhi Decoctions,Results show that the contents change with different decoctions.