��Ⱦľ����������������λ��ѧ�ɷ��о�

??OBJECTIVE To study the chemical constituents of the ethyl acetate fraction from the stems of Saprosma merrillii Lo. METHODS The compounds were isolated and purified by silica gel column and Sephadex LH-20 column. Their structures were elucidated on the basis of chemical properties and spectral analysis. RESULTS Ten compounds were isolated and elucidated as 5-hydroxylmethylfuraldehyde(1), 3??-hydroxycholesta-5-ene(2), scopoletin(3), isoscopoletin(4), quercetin-3-O-glucoside-6??-gallate(5), 4??-hydroxy-7-methoxy flavanone(6), pinoresinol(7), N-trans-coumaroyltyramine(8), luteolin-7-O-B-D-glucopyranoside(9), and hypodiolide A(10). CONCLUSION All of the compounds are isolated from this genus for the first time except for compound 3     

CYP3A4*18A��CYP3A4*18B��MDR1 C3435T�����̬�Զ԰��з���͡ѪҩŨ�ȼ���Ч��Ӱ��

??OBJECTIVE To investigate the interindividual variabilities of plasma concentration and lipid-regulating efficacy of atorvastatin in patients with hyperlipidemia through the genotyping of CYP3A4*18A, *18B and MDR1 C3435T genes.METHODS One hundred and fifteen Chinese Han population with hyperlipidemia were genotyped by the PCR-RFLP (restriction fragment length polymorphism).The steady-state plasma trough concentrations of atorvastatin were measured by high performance liquid chromatography (HPLC)-UV.The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were monitored by the homogeneous enzyme method before treatment and 1 month after medication.RESULTS The mutation frequencies of CYP3A4*18A,*18B and MDR1 C3435T were 3.48%,23.48% and 31.74% respectively.It shows no statistically significant difference for the SNPs frequencies between the normal population reported and patients selected.Patients with CYP3A4*18B homozygous mutant (AA) showed a significantly higher plasma concentration of ATV compared with the G/A heterozygous mutat patients or the G/G wild-type homozygous (P=0.016).However,no significant difference could be shown in the patients with CYP3A4*18A and MDR1 C3435T genotypes(P??0.05).Neither CYP3A4*18A nor MDR1 C3435T could be shown a significant difference in the lipid lowering efficiency(P>0.05).Patients carrying the homozygous mutant (AA) of the CYP3A4*18B gene showed a significantly higher TC lipid-regulating effect compared with patients with the GA or GG genetic variant (P=0.02). The LDL-C change rates among the three genotype groups were significantly different, with AA group >GA group >GG group (P=0.01) and the regulation of TG and HDL-C for AA,GA or GG was compared without finding any significant difference (P>0.05).The TC changerates and plasma concentration were significantly correlated (P=0.031) before and after treatment,while there was no statistical significance in the correlation of the other three lipid change rates with plasma concentration (P??0.05).CONCLUSION The SNPs MDR1 C3435T and CYP3A4*18A do not affect the plasma concentration and efficacy of ATV. In ATV therapy, patients with the CYP3A4*18B gene exhibit higher plasma concentrations than the non-carriers, and the lipid-lowering efficacy was more pronounced.     

��-���ݶ���TxID���ǻ���ͬ��Ȧ�3��4��������������������о�

??OBJECTIVE To interrogate differential sensitivity of ??-conotoxin TxID on stoichiometry of ??3??4 nicotinic acetylcholine receptors(nAChRs). METHODS Oocytes of Xenopus laevis were used to express rat ??3??4 nAChRs with different stoichiometries by altering ??3:??4 RNA injection ratios of 1:1, 1:10 or 10:1. Sensitivity of ??-conotoxin TxID on these different stoichiometry receptors were evaluated and compared. RESULTS The three stoichiometry receptors of ??3??4 nAChRs were expressed in oocytes successfully. ??-Conotoxin TxID showed differential sensitivity on ??3??4 nAChR stoichiometries. Inhibition of 1:10 injection ratio by TxID was similar with regular 1:1 ??3??4 nAChRs within 2-fold difference. While potency of 10:1 injection ratio by TxID decreased 5-fold significantly comparing with 1:1 ??3??4 nAChRs. CONCLUSION ??-Conotoxin TxID exhibits distinct sensitivity on different stoichiometry of ??3??4 nAChRs, which could reflecting different stoichiometries of ?? and ?? subunits. The RESULTS would be helpful for elucidation of structure and physiology function of ??3??4 nAChRs.     

五味子成分对CYP3A4的抑制作用

日本药学会第123次年会于2003年3月27～29日在日本长崎县召开。现对本次年会中有关天然药物方面的研究文献摘要予以介绍,供国内研究人员参考。     

��ѡ�����������弤����5��-N-�һ����������յ������ļ��������ü�������о�

??OBJECTIVE To study the roles of adenosine A2A and A2B receptor in 5??-(N-ethylcarboxamido) adenosine (NECA)-induced cardioprotection in vitro against reperfusion injury, and to explore the underlying mechanism. METHODS Simulated ischemia/reperfusion injury model was developed in cardiac H9c2 cells. NECA, an unselective adenosine receptor agonist, the selective antagonists of adenosine A2A receptor antagonist SCH58261 (SCH) and the selective A2B receptor antagonist MRS1706 (MRS) were used. CCK-8 assay was used to evaluate cell viability. Mitochondrial membrane potential (????m) was measured with fluorescence microscope using JC-1. Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit was used to detect the level of intracellular H₂O₂. Intracellular reactive oxygen species (ROS) levels were determined with DCFH-DA. Mitochondrial ROS were detected with MitoSox Red. RESULTS NECA applied at reperfusion reduced cell death in cells subjected to simulated ischemia/reperfusion. Compared with the ischemia/reperfusion injury group, NECA inhibited the reduction of cell viability and ????m, and the elevation of intracellular and mitochondrial ROS, which were all abolished by adenosine A2A and A2B receptor antagonists(P<0.01 or P<0.05 ). CONCLUSION Adenosine A2A and A2B receptors work in concert to mediate the cardioprotective effect of NECA presumably by modulating the mPTP opening and mitochondrial ROS generation.
     

UPLC-MS������������΢����CYP1A2��CYP2D1ø��л���Ա���������ѧ�о�

??OBJECTIVE To establish a robust, fast and convenient method for in vitro assay of rat liver CYP1A2 and CYP2D1, and explore their kinetic features.METHODS Two selective substrates including phenacetin and dextromethorphan, which are probes of CYP1A2 and CYP2D1, were chosen for liver microsomes incubation, respectively; the corresponding ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS) methods were developed for kinetic studies.RESULTS The fast and convenient UPLC-MS methods with high resolution and short running time(4~5 min) were established and validated for two assays of CYP1A2 and CYP2D1 activities;both methods showed good accuracy and precision, and the values of LOQ for CYP1A2 and CYP2D1 assays could reach 0.267 and 0.007 ??mol??L^-1, respectively. The kinetic studies showed that the Michaelis constant(K_m) for CYP1A2 and CYP2D1 were (28.4??2.7) and (13.9??1.3) ??mol??L^-1, respectively. Their activities were determined to be (1.47??0.12) and (3.98??0.09) nmol??mg^-1, respectively,when the substrate concentration was 10 ??mol??L^-1.CONCLUSION UPLC Tandem MS technique is proved to be a rapid, convenient and efficient approach with high sensitivity and selectivity for the assays of CYP1A2 and CYP2D1 in drug metabolism.     

�²˸��Ļ�ѧ�ɷ��о�

??OBJECTIVE To investigate the chemical constituents in the roots of Allium tuberosum. METHODS Colum chromatography with different materials such as silica gel was used to isolate and purify the chemical constituents. Their structures were identified by spectroscopic analysis. RESULTS Nine compounds were isolated from the roots of Allium tuberosum and their structures were identified as 4,8-dihydroxyacetophenone-8-O-ferulate(1), 4,8-dihydroxyacetophenone(2), 3,4,5-trimethoxybenzoic acid(3), 3,4,5-trimethoxycinnamic acid(4), buddlenol D(5), E-1,6,11-triene-4,5,9-trithiadodeca-9,9-dioxide(6), tianshic acid(7), daucosterol(8), and linoleic acid(9). CONCLUSION Compound 1 is a new compound and compounds 2-5 are obtained from Allium tuberosum for the first time.     

��ͩ����ѧ�ɷ��о�

??OBJECTIVE To investigate the chemical constituents in flowers of Paulownia fortunei (Seem.) Hemsl. METHODS The flowers of Paulownia fortunei (Seem.) Hemsl. were extracted with 50% aqueous acetone by tissue disruption extraction. The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, Sephadex LH-20, MCI Gel CHP-20, silica gel column chromatography and preparative HPLC, and their structures were elucidated on the basis of spectral data and physiochemical properties. RESULTS Nineteen compounds were elucidated as 2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol(1), 1-phenylpropane-1,2,3-triol(2), 3,4-dihydroxy-β-methoxyphenethy alcohol(3), chryseriol(4), phenylpropanoid(5), apigenin(6), luteolin(7), 4-hydroxy-3-methoxybenzoic acid(8), 2-(4-hydroxyphenyl) ethanol(9), 3,4-dihydroxyphenylethyl alcohol(10), vanillic acid(11), 3-(4-hydroxy-3,5-dimethoxyphenyl) propane-1,2-diol(12), p-hydroxybenzoic acid(13), astragalin(14), nicotinic acid(15), thymidine(16), thymine(17), 5-(4′-hydroxybenzyl) hydantoin(18) and 1-(3-indolyl)-2,3-dihydroxypropan-1-one(19). CONCLUSION Compounds 1-3, 5, 8-10, 12, 14-19 are isolated from this plant for the first time.     

�׻��ܽ��ݵ�ľ֬���໯ѧ�ɷ��о�

??OBJECTIVE To study the chemical constituents of Patrinia villosa (Thunb.) Juss. METHODS The compounds were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, Sephadex LH-20, and reversed-phase HPLC. Their structures were elucidated by physiochemical property and spectral analysis. RESULTS Eleven compounds were isolated and identified as(7R,8S)-3,3??,5-trimethoxy-4??,7-epoxy-8,5??-neolignan-4,9,9??-triol-9-O-??-D-glucopyranoside(1), massonianoside D(2),(7R,8S)-dihydroxydehydrodiconiferyl alcohol-4-O-??-D-glucopyranoside(3),(7S,8R)-dihydroxydehydrodiconiferyl alcohol-4-O-??-D-glucopyranoside(4), 7R,8S-glochidioboside(5), lariciresinol-4-O-??-D-glucopyranoside(6), lariciresinol-9-O-??-D-glucopyranoside(7), lariciresinol-4??-O-??-D-glucopyranoside(8), tortoside B(9), tanegool(10), and tanegool-7??-methyl ether(11). CONCLUSION All compounds are isolated from Patrinia genus for the first time.     

��ҩ�����ﻯѧ�ɷ��о�

??OBJECTIVE To study the chemical constituents of the chloroform extract from the aerial parts of Artemisa sacrorum. METHODS The chemical constituents were isolated and purified by silica gel and LH-20 column chromatography and preparation HPLC. Their structures were identified by spectral analysis methods. RESULTS Thirteen compounds were obtained and identified as 5-hydroxyl-7,4??-dimethoxyflavone(1), 4-hydroxylacetophenone(2), 5,4??-dihydroxyl-7,3??-dimethoxyflavone(3), 5,7-dihydroxyl-6,4??-dimethoxyflavone(4), 5,7-dihydroxyl-4??-methoxyflavone(5), 5,4??-dihydroxyl-7-methoxyflavone(6), caffeic acid(7), 8-hydroxyl-6,7-dimethoxycoumarin(8), 3,4-dihydroxylbenzoic acid(9), acetophenone-4-O-??-D-glucoside(10), 6-methoxycoumarin-7-O-??-D-glucoside(11), 6,8-dimethoxycoumarin-7-O-??-D-glucoside(12), and 2-hydroxyl-6-methoxyacetophenone-4-O-??-D-glucoside(13). CONCLUSION Compounds 3, 4, 5, 9, 10 and 12 are isolated from this plant for the first time.
     

CYP3A5和MDR1基因多态性与肝移植病人他克莫司浓度/剂量比的关系

 目的研究肝移植术后患者的细胞色素P4503A5酶(CYP3A5)和多药耐药蛋白(MDR1)基因多态性对他克莫司浓度/剂量比的影响。方法记录患者的体重、他克莫司剂量和血药浓度等指标,采用聚合酶链式反应-限制性内切片段长度多态性(PCR-RFLP)方法对肝移植患者进行基因分型,比较不同基因型患者之间他克莫司的浓度/剂量比。结果CYP3A5*1/*1和*1/*3型患者的他克莫司浓度/剂量比明显低于*3/*3型患者(P<0.01),MDR1的3435和2677位点各基因型分组之间无明显差异(P>0.05)。结论CYP3A5基因*3多态性与他克莫司血药浓度/剂量比具有显著相关性,*1/*1和*1/*3型的患者拟取得相似的血药浓度要比*3/*3型患者服用更高剂量的他克莫司,用药前检测基因型可以更有效地对他克莫司进行剂量调整。     

心脏移植患者环孢素 A 药动学研究

 目的 荧光偏振免疫法测定心脏移植患者连续服用环孢素 A 至稳态后的血药浓度并考查其药动学特点 。 方法 采用荧光偏振免疫法测定 5 名心脏移植术后患者服药达稳态后单剂量 <> po 环孢素 A 每次 100 mg , bid 后药物在体内的经时过程 。 结果 5 名心脏移植术后患者环孢素 A 的 <> t _max 为 (1.60 ± 0.55)h ; <> ρ _max 为 (951.60±229.20) μg·L^-1 , <> t _1/2 为 (6.53±2.40)h , AUC_0~t 为 (5 162.10 ± 1 355.01) μg·h·L^-1 。 结论 建立中国心脏移植患者环孢素 A 的稳态药动学参数 。     

ABCB1和CYP3A5基因多态性对环孢素血药浓度的影响

 目的 研究ABCB1基因和CYP3A5基因多态性与重症肌无力患者环孢素药物浓度的关系。方法 在129名重症肌无力(MG患者中,采用荧光PCR法测定ABCB1 C3435T基因型;RFLP法分析ABCB1 C1236T, ABCB1 G2677A/T;Mismatch RFLP(错配PCR+RFLP法分析CYP3A5*3基因型,并对这4个位点进行连锁分析。收集患者临床资料,对患者环孢素血药浓度进行检测,并对患者遗传学数据和血药浓度等进行分析。结果 连锁分析显示4个SNP中,ABCB1 C1236T,G2677A/T和C3435T之间紧密连锁,ABCB1中最常见的两个单倍体型分别是1236C-2677G-3435C和1236T-2677T-3435T。另外发现CYP3A5*1/*3位点、ABCB1 C1236T位点和ABCB1 G2677T位点的多态性变化对环孢素血药浓度有明显影响,突变型组的血药浓度明显比野生型组高。同时根据ABCB1单倍体型分组,各组之间药物浓度比较都是TT-TT-TT> CT-GT-CT > CC-GG-CC。结论 药物基因学研究对环孢素治疗重症肌无力患者的临床合理用药有指导意义。     

他克莫司在151例肝移植受者的常规监测的群体药动学研究

 目的考察国人肝移植受者口服他克莫司(Tacrolimus,FK506)常规监测的群体药动学特征,为实施个体化用药提供新途径。方法收集151例肝移植受者FK506的血药浓度数据,应用非线性混合效应法(NONMEM)选择药动学模型和统计学模型,并考察性别(GEN)、年龄(AGE)、体重(BW)、术后时间(POD)、剂量(DOSE)、合并用药、肝肾功能、红细胞压积(HCT)等协变量对药动学参数的影响,建立最终回归模型。并根据Bayesian反馈估算获得个体和群体的药动学参数以及预测血药浓度。结果NONMEM法对151例肝移植受者的总数据集用一级吸收二房室开放模型进行拟合,指数模型表征个体间和个体自身变异。将总数据集随机分为建模组和验证组。用建模组数据获得的群体参数在验证组中有较理想的拟合优度。群体药动学参数为:CL为19 L·h^-1,V2为170 L,Q为71 L·h^-1,V3为324 L,K_a为2.670 h^-1,吸收延迟时间(ALAG)为0.230 h。协变量对药动学参数的影响按照OB J下降的幅度依次为DOSE,BUN,HCT对CL;BUN,DOSE,AGE对V2。经Bayesian反馈得到的预测浓度和实测浓度的相关性为r=0.97。模型的误差分析结果表明,平均绝对权重残差(MAWR)为(11±10)%。结论NONMEM法建立回归模型能较好地估算应用FK506的肝移植受者的个体及群体药动学参数,应用回归模型并利用Bayesian反馈可用于临床个体化给药。     

盐酸小檗碱对心脏移植受者环孢素A药代动力学影响

目的观察联合应用盐酸小檗碱(黄连素,berberine hydrochloride,BBR)对心脏移植受者服用环孢素A(Cyclosporine,CsA)药代动力学的影响。方法选取心脏移植长期存活(>1年)受者15例,年龄18～65岁,体重45～78 kg,无肝肾功能异常。受者在原有免疫抑制方案基础上服用BBR 0.3 g/d(分3次服用),在加药前1天和加药后第14天的不同时间点各检测全血CsA血药浓度。采血时间点分别为服药前(0 h)和服药后0.25 h,期函数0.5、0.75、1.0、1.5、2.0、3.0、4.0、6.0、8.0、10.0、12.0(h)。观察合用BBR前后CsA浓度、药代动力学参数和生化指标[血清总胆红素(TBIL)、谷丙转氨酶(ALT)、血浆总蛋白(TP)、尿素氮(BUN)、肌酐(Cr)]的变化。结果在合用BBR后吸收相(0～0.75 h)及消除相(3～12 h)CsA全血浓度均较合用前明显增高(P<0.05)。合用BBR后血药浓度-时间曲线下面积(AUC_0～12h)平均增加(33.49±20.72)%,达峰时间(t_max)延迟(均P<0.05)。合用BBR前后TBIL、ALT、TP、BUN、Cr比较,差异无统计学意义(P>0.05)。结论联合应用BBR与CsA后,可以使CsA的达峰时间(t_max)延迟,半衰期(t_1/2)延长,清除率减少,AUC增大,生物利用度增加;减少CsA的服用剂量,且无明显不良反应。     

Effect of Chinese herbs on CYP3A4 activity and expression in vitro

Ethnopharmacological relevance

Traditional Chinese Medicine (TCM) has become more popular among cancer patients in the Western world, who often use Chinese herbs as adjuvant therapy to reduce the adverse effects of conventional chemotherapy. However, pharmacokinetic (PK) interactions between Chinese herbs and anticancer drugs can occur and have dramatic consequences for these patients. Currently, only a few possible PK interactions between Chinese herbs and conventional Western drugs have been documented.

Aim of the study

Since the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) contributes to most of the PK interactions with (anticancer) drugs, the effect of four Chinese herbs (Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus) on the activity and expression of CYP3A4 was investigated in vitro.

Materials and methods

Ethanol and water–ethanol extracts of the four Chinese herbs were prepared from raw material. CYP3A4 inhibition was assessed by the use of Supersomes^™ in a fluorescence assay. Furthermore, CYP3A4 induction was evaluated in a human pregnane X receptor (hPXR)-mediated CYP3A4 reporter gene assay and a quantitative real time PCR assay, both in human colon adenocarcinoma-derived LS180 cells (LS180).

Results

Extracts of Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus inhibited CYP3A4 in human CYP3A4 Supersomes^™ (IC₅₀ values: 17–83 µg/mL). Oldenlandia diffusa and Rehmannia glutinosa significantly induced PXR-mediated CYP3A4 (p<0.001). Oldenlandia diffusa also significantly induced CYP3A4 mRNA levels (p<0.001 at 250 µg/mL).

Conclusions

Concomitant use of Oldenlandia diffusa and Rehmannia glutinosa could result in induction of CYP3A4, leading to a reduced efficacy of drugs that are CYP3A4 substrates and have a narrow therapeutic window. Because of the possible enhanced toxicity caused by CYP3A4 inhibition, clinical effects of CYP3A4 inhibition by Astragalus propinquus and Codonopsis tangshen must also be taken into account. In conclusion, herb–drug interactions between Chinese herbs and various CYP3A4 substrates can occur. Further research to investigate the clinical relevance of the interactions caused by Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus propinquus is required.     

供体CYP3A5基因多态性影响肝移植术后FK506的个体化用药

 目的探讨肝移植术后口服免疫抑制剂FK506的剂量及其全血谷浓度的个体差异与供体的肝药酶P450 3A5(CYP3A5)基因多态性的关系。方法观察44例接受肝移植的受体在术后1,2周及1月的FK506服药剂量和全血药物谷浓度,并利用PCR-限制性片断长度多态性(PCR-RFLP)方法和DNA直接测序法检测对应供体CYP3A5基因内含子3第6 986位A/G单核苷酸多态性(CYP3A5*3),分析基因多态性与FK506服用剂量及全血谷浓度/剂量比值(C/D)的相关性。结果肝移植术后FK506的口服需药量在个体间存在极大差异,在术后2周及1月,CYP3A5*3/*3基因型患者需要的剂量最小,分别为(0.074±0.042)和(0.084±0.045)mg·kg^-1·d^-1,而C/D比值明显高于*1/*1基因型患者。结论肝移植术后受体FK506服用剂量的个体化差异与供体CYP3A5*1/*3基因多态性密切相关,分析供体CYP3A5*1/*3基因多态性可以为肝移植术后FK506的个体化用药提供可靠的参考指标。     

健康志愿者多剂量服用左金丸对CYP3A4活性的影响

目的研究健康受试者口服左金丸对细胞色素P450酶3A4(CYP3A4)活性的影响。方法采用随机开放两周期试验设计,16名健康受试者(男女各半)口服左金丸7 d(每天2次,每次3 g)前、后再分别单剂量口服咪达唑仑15 mg,LC-MS/MS测定咪达唑仑及其代谢物1-羟基咪达唑仑在24 h内不同时间点的血药浓度,Win Nonlin软件计算咪达唑仑及1-羟基咪达唑仑的主要药代动力学参数。结果服用左金丸前后,受试者血浆中咪达唑仑的Cmax分别为(138.44±62.55)ng/m L、(132.99±64.74)ng/m L;AUC0-24分别为(305.25±112.05)ng·h/m L、(343.68±149.39)ng·h/m L;tmax分别为(0.5,0.25-2)h、(0.5,0.25-3)h;t1/2分别为(3.52±1.06)h、(3.99±1.30)h;清除率(CL/F)分别为(54.65±17.65)L/h、(49.74±17.88)L/h;Cmax代谢比分别为(0.60±0.24)、(0.42±0.18);AUC0-24代谢比分别为(0.53±0.18)、(0.41±0.14)。结论口服左金丸7 d对CYP3A4有弱抑制作用。     

建立一种测定细胞色素P450 3A4活性的方法

 目的建立一种细胞色素P450 3A4(cytochrome P450 3A4,CYP3A4)活性定量的新方法。方法将CYP3A4底物硝苯地平与人肝微粒体进行体外温孵,以高效液相色谱法测定硝苯地平及其氧化产物,以甲醇-水(64∶36)为流动相,流速为0.5 mL·min^-1,检测波长为254 nm。结果在所建立的HPLC条件下,硝苯地平及其氧化产物的出峰时间分别在8.44和6.15 min,能够完全分离,且无其他生物基质峰干扰;氧化硝苯地平在人肝微粒体的最低检测限为25μg·L^-1(S/N=3),线性范围是0.25～32 mg·L^-1(r=0.999 4),符合检测要求;在0.5,4.0,20.0 mg·L^-1时的萃取率分别为(67.05±3.49)%,(66.63±3.60)%,(67.08±2.78)%(n=5);方法回收率分别为(100.17±6.97)%,(91.96±3.71)%,(96.55±3.98)%(n=5);日内及日间RSD均小于7%。结论本实验所建立的HPLC能够准确、快速检测出硝苯地平及其在人肝微粒体中的氧化产物,能够对CYP 3A4活性进行快速评价,适合于体外药物代谢动力学研究和第三代多药抗药性逆转剂的筛选。