萘哌地尔在大鼠体内的药代动力学

为全面了解萘哌地尔(Naf)在大鼠体内的代谢过程,用反相HPLC-UV法,给大鼠ig10,20,30mg·kg^-1Naf后,测定在不同时间各组织和体液中Naf的含量。结果表明,Naf在大鼠体内药代动力学为二室模型,T_1/2α为0.47～1.01h,T_1/2β为4.78～7.08h,达峰时间T(peak)为0.42～0.90h,Cmax,AUC随剂量升高而增大。给药后15min,肠壁组织浓度最高,其次为肝、肺;2h以后,除睾丸、卵巢和子宫外,其余组织药物浓度逐渐降低。尿、粪及胆汁中原形药总排出量不足给药量的1%,提示Naf在大鼠体内有首过效应及代谢物生成。在100～500mg·ml^-1浓度范围内,Naf血浆蛋白结合率为82%～97%。     

泻心汤黄酮类成分在大鼠体内的药代动力学研究

研究泻心汤中黄酮类成分在大鼠体内药代动力学规律。大鼠灌胃给予泻心汤12 g·kg^-1，给药前及给药后不同时间采集血样或尿样，HPLC法测定黄酮类成分浓度，血药浓度-时间数据和尿药排泄量-时间数据用DAS软件进行动力学分析。采用大鼠肾匀浆温孵法，进行黄芩苷的体外代谢研究。结果显示,黄芩苷、汉黄芩苷血药浓度迅速达峰，药时曲线呈现双峰现象，消除T_1/2均为6 h左右；黄芩苷、汉黄芩苷、黄芩素、汉黄芩素在尿中均有排泄，尿中排泄量占给药量均<10%，尿排泄T_1/2在6～8 h；大鼠肾匀浆可将黄芩苷代谢生成黄芩素，酶动力学参数V_max＝702 nmol·min^-1·g^-1(protein)，K_m＝135 μmol·L^-1。可见，泻心汤中黄酮类成分可迅速吸收进入体内；黄芩苷、汉黄芩苷、黄芩素、汉黄芩素均可从尿排泄，但尿药排泄量较少；肾脏可将黄芩苷代谢成黄芩素。     

疾病以及配伍对人参皂苷在大鼠体内的药动学影响

目的 建立SD大鼠血浆中人参皂苷Rb1、Rb2和Rg1的HPLC分析方法,对比分析配伍白术挥发油前后,人参皂苷在慢性萎缩性胃炎模型大鼠体内药动学特征。方法 SD大鼠分为4组,其中单用正常组和单用模型组均给药人参总皂苷292 mg·kg^-1,配伍正常组和配伍模型组均给药人参总皂苷292 mg·kg^-1和白术挥发油0.1 mL·kg^-1。于给药前和给药后不同时间点进行眼眶取血,采用HPLC测定各成分的血药浓度,并采用Winnolin 6.3软件计算其药动学参数。结果 与单用正常大鼠比较,单用模型组大鼠体内人参皂苷Rb1的C_max和AUC值降低,T_max、T_1/2以及MRT增加,人参皂苷Rb2和Rg1则呈现出AUC增加的变化;而配伍正常组大鼠体内人参皂苷Rb1、Rb2和Rg1的C_max和AUC值均增加,T_max、T_1/2以及MRT值均缩短。与单用模型组大鼠比较,配伍模型组大鼠体内人参皂苷Rb1和Rg1的C_max和AUC值均增加,T_max、T_1/2以及MRT值均降低。结论 在相同给药剂量下,疾病状态机体对人参皂苷的吸收和代谢呈现缓慢趋势,而配伍后能促进皂苷成分在体内的吸收,同时加快代谢消除,为人参的临床用药提供参考依据。     

杜鹃素在大鼠体内的药动学研究

目的 研究杜鹃素在正常大鼠体内的药动学特征。方法 杜鹃素单剂量ig给予大鼠后,采用HPLC法测定给药后不同时间点大鼠血浆中的杜鹃素,通过DAS软件程序模拟计算,得出杜鹃素在大鼠体内相应的药动学参数。结果 杜鹃素在大鼠体内的药动学模型符合二室模型,主要药动学参数为：t_1/2α＝（0.33±0.10）h,t_1/2β＝（15.22±8.98）h,CL/F＝（14.89±3.45）L/(h?kg),C_max＝（1.61±0.14）mg/L,T_max＝（0.25±0.01）h,MRT_(0-t)＝（2.35±0.08）h,AUC_(0-t)＝（3.06±0.16）mg?h/L。结论 本研究建立的HPLC方法专属性强,简便、准确,可用于杜鹃素在大鼠体内的药动学研究;大鼠ig给予杜鹃素后,其在血浆中分布较快,半衰期较短。     

氢化阿托酸在大鼠体内立体选择性时间药代动力学

以余弦法分析氢化阿托酸(HTA)药代动力学参数证明,下列参数具有昼夜节律:标准明暗周期下,S(+)-HTA的T_1/2β和CL,R(-)-HTA的T_1/2β以及外消旋体的CL和MRT;反相明暗周期下,S(+)-HTA的T_1/2β和AUC,R(-)-体的CL以及外消旋体的CL。下列参数具有立体选择昼夜节律:标准明暗周期下,S(+)-HTA的CL,反相明暗周期下,S(+)-HTA的T_1/2β和AUC以及R(-)-HTA的CL。以外消旋体给药后,大鼠体内由R(-)-体向S(+)-体的转化过程,可出现昼夜节律,在两种明暗周期下,峰值相位均位于黑暗期之末,据此,提出HTA的清晨给药治疗方案。     

盐酸西布曲明在中国志愿者体内的药代动力学

目的研究西布曲明主要药理活性代谢产物N-去二甲基西布曲明（BTS 54505）在中国志愿者体内的药代动力学。方法20名健康中国志愿者采用随机交叉自身对照的方式，单剂量po盐酸西布曲明胶囊20 mg。给药后，连续采集血样至72 h。分离得到的血浆，采用高效液相色谱-电喷雾-二级质谱分析BTS 54505的血药浓度。结果国产和进口胶囊剂的体内药代动力学参数AUC_0-t，AUC_0-∞，C_max，T_max,T_1/2,Kelm和MRT均与文献报道相似。结论国产和进口胶囊剂生物等效。     

萘普生胆碱离子液体在大鼠体内的药动学及生物利用度研究

目的 研究萘普生胆碱离子液体灌胃给药后在大鼠体内的药动学和生物利用度。方法 采取灌胃给药的方式给予大鼠萘普生胆碱离子液体,于给药后不同时间点采集血样,血样经甲醇沉淀蛋白后离心,采用Extend-C₁₈色谱柱（4.6 mm×250 mm,5 μm）,甲醇（A）-0.3%磷酸水溶液（B）（74：26）为流动相,流速为0.8 mL·min^–1,检测波长为230 nm,以吲哚美辛为内标液,萘普生为测定对象,分析大鼠体内血浆中萘普生胆碱离子液体的浓度。应用DAS 2.0软件拟合药动学参数。结果 大鼠灌胃给药萘普生混悬剂后t_1/2α为5.12 h,t_1/2β为10.13 h,T_max为2 h,C_max为112.92 mg·L^–1,AUC_（0-t）为1 091.01 mg·L^–1·h;大鼠灌胃给药萘普生胆碱离子液体后t_1/2α为5.64 h,t_1/2β为69.32 h,T_max为1 h,C_max为135.97 mg·L^–1,AUC_（0-t）为1 305.79 mg·L^–1·h,相对生物利用度为119.686%。结论 大鼠灌胃萘普生胆碱离子液体后,萘普生达峰时间提前,达峰浓度和生物利用度均高于萘普生混悬剂。     

片剂释放度研究——四种测定方法的比较

本实验收集了国内阿司匹林生产样品五种及原料一种,作为典型药品进行了四种方法(杯法,崩解仪法,转篮法及循环法)的体外测定并测定了体内狗血药水平,将体内外测定结果进行了统计分析。以T₅₀%(中位数时间),T_d(特征时间63.2%)及m(斜率)三个参数和体内的T_max(高峰时间),C_max(高峰浓度)及血药水平时间曲线下面积A_uc三个参数作F检验,认为在各方法之间有显著性差异,并且循环法的灵敏性较好,但变异系数以杯法最小,体内外有一定的相关。     

麝香酮在大鼠、家兔和狗体内的药代动力学

麝香酮在大鼠体内的药时过程符合二室开放模型,在家兔和狗体内的药时过程则符合三室开放模型。大鼠、家兔和狗之间的药代动力学过程存在着显著的种属差异,大鼠iv麝香酮12,18和24 mg/kg三种剂量间的药代动力学主要参数无显著性差异。iv给药大鼠的T_1/2B为118.1～131.2min。家兔和狗的T_1/2B分别为24.9和30.0 min,T_1/2γ分别为331.9和366.4 min。大鼠、家兔和狗三b种动物的V_ss分别为23.0,51.7和7.3 L/kg.V_c分别为2.33,2.13和0.38 L/kg。     

前列腺素E1经不同途径给药后的大鼠体内药效学比较

本文研究了前列腺素E₁(PGE₁)分别经不同途径给药后的大鼠体内药效学，旨在寻找目前PGE₁注射给药的替代途径。以PGE₁降压效应作为药效学指标，以静脉注射为对照，分别测定PGE₁经鼻腔、舌下、肌肉(im)、腹腔(ip)给药后的药效学参数，包括峰效应时间(Tmax)，血压下降最大百分数(Emax，%)，效应持续时间(T_d)以及血压下降百分数-时间曲线下面积(AUC，%·min)。研究结果表明，PGE₁经上述途径给药后，药效学参数Emax，T_d，AUC等均随给药剂量的增加而增大，提示存在明显的剂量-效应关系。根据所测Tmax值，推断上述给药途径其吸收速率的大小顺序为：鼻腔≈im>ip>舌下；依据所测药理生物利用度(PF)值，预测药物绝对生物利用度的顺序为：鼻腔>im≈ip>舌下。上述研究结果提示，PGE₁经鼻腔与舌下黏膜给药，有望替代目前的注射给药。     

(-)threo-chlorocitric acid decreases sham feeding of sucrose in rats.

The contribution of changes in rate of gastric emptying to the anorectic effect of (-)-threo-chlorocitric acid (chlorocitrate) was assessed by examining the effect of this drug in sham feeding rats, a preparation where gastric distention does not occur. Gavage administration of chlorocitrate (100-400 mg.kg-1) decreased sham and real feeding of 20% sucrose in a dose-related manner. In sham-feeding rats, the minimal effective dose was 200 mg.kg-1. The anorectic effect was evident at 60 min after 200 mg.kg-1 and 30 min after 400 mg.kg-1. In real-feeding rats, the minimal effective dose was 100 mg.kg-1 and for all doses tested the effect was apparent at the 15-min time point. In a second experiment, the effect of chlorocitrate (100-400 mg.kg-1) on gastric emptying of 20% sucrose was examined. Chlorocitrate (200 and 400 mg.kg-1) had a modest but significant inhibitory effect on gastric emptying; however, the effect was not dose-related. Inasmuch as chlorocitrate decreased sham feeding, its anorectic effect cannot be solely attributed to inhibition of gastric emptying. However, because chlorocitrate was more potent in the real-feeding condition relative to sham feeding, and the time course of the response in the two feeding conditions was different, part of chlorocitrate's anorectic effect may depend on postingestive cues such as gastric distention.     

Pharmacokinetics of dexloxiglumide after administration of single and repeat oral escalating doses in healthy young males

OBJECTIVE: To assess the pharmacokinetics, safety and tolerability of dexloxiglumide, a new CCK1 receptor antagonist currently under development for the treatment of the constipation-predominant irritable bowel syndrome. SUBJECTS AND METHODS: Twelve volunteers were enrolled in the present study and received orally 100, 200 and 400 mg of dexloxiglumide as tablets as a single dose followed by repeated t.i.d. doses for 7 days according to a randomized, double-blind, double-dummy complete crossover design. Plasma and urine were collected before drug administration and up to 72 h after dosing. Dexloxiglumide plasma and urinary concentration, determined using validated HPLC methods with UV detection, were used for the pharmacokinetic analysis by standard noncompartmental methods. In addition, dexloxiglumide safety and tolerability were evaluated throughout the study period by performing standard laboratory tests, by recording vital signs and ECGs and by monitoring the occurrence and severity of adverse events. RESULTS: After a single oral administration, dexloxiglumide was rapidly bioavailable with mean t(max) ranging from 0.9 - 1.6 h at all doses. The mean peak plasma concentrations (Cmax) were 1.7+/-0.6, 5.4+/-1.7, and 11.9+/-4.7 microg/ml, and the mean area under the plasma concentration-time curves (AUC) were 4.4+/-3.3, 8.6+/-3.6, and 18.3+/-5.9 microg x h/ml at the 3 doses, respectively. Apparent plasma clearance (CL/F) was 30.8+/-13.9, 27.2+/-10.6, and 21.1+/-8.6 l/h at the 3 doses, respectively. The apparent elimination half-life from plasma (t1/2) ranged from 2.6 - 3.3 h at the 3 doses. The excretion of unchanged dexloxiglumide in 0 - 72 h urine accounted for approximately 1% of the administered dose and this was true for all doses. Dexloxiglumide renal clearance (CLR) averaged 0.4+/-0.4, 0.4+/-0.2, and 0.3+/-0.3 l/h for the 3 doses, respectively. After the last dose of the repeated dosing period dexloxiglumide Cmax occurred at 1.1 - 1.6 h after drug administration and averaged 2.4+/-1.3, 7.1+/-2.9, and 15.3+/-2.7 microg/ml for the 3 doses, respectively. The AUC values averaged 5.9+/-3.0, 16.0+/-8.8, and 50.8+/-38.1 microg x h/ml, respectively. The area under the plasma concentration-time curve calculated at steady state within a dosing interval (AUCss) averaged 4.6+/-1.6, 11.3+/-3.6, and 28.4+/-8.2 microg x h/ml, whereas CL/F averaged 20.3+/-8.3, 16.3+/-9.0, and 10.3+/-5.0 l/h at the 3 doses, respectively. Dexloxiglumide t1/2 could not be accurately calculated due to the high inter-subject variability and to sustained dexloxiglumide plasma concentrations that precluded the identification ofthe terminal phase of the plasma concentration-time profiles. However, it appeared that dexloxiglumide t1/2 was considerably prolonged at the dose of 400 mg. CLR averaged 0.4+/-0.4, 0.3+/-0.3, and 0.3+/-0.1 l/h for the 3 doses, respectively. After a single dose, the plasma pharmacokinetics of dexloxiglumide were dose-independent in the dose range 100 - 400 mg. After repeated dose the pharmacokinetics of dexloxiglumide were virtually dose-independent in the dose range 100 - 200 mg. A slight deviation from linear pharmacokinetics was found with a dose of 400 mg. Dexloxiglumide plasma pharmacokinetics were also time-independent in the dose range 100 - 200 mg with a deviation from expectation based on the superimposition principle with a dose of 400 mg. Dexloxiglumide urinary excretion and renal clearance were both dose- and time-independent in the dose range 100 - 400 mg. The safety and tolerability of dexloxiglumide administered to healthy young males was good up to the maximum investigated dose of 400 mg both after single and after repeated doses. CONCLUSIONS: The safety and pharmacokinetic profile of dexloxiglumide when the drug is administered as single and repeated doses in the dose range 100 - 400 mg provides the rationale for the choice of the treatment schedule (200 mg t.i.d.) for the efficacy trials in patients with (constipation-predominant) irritable bowel syndrome.     

The pharmacokinetics and pharmacodynamics of quinidine and 3-hydroxyquinidine.

1. The pharmacokinetics and pharmacodynamics of quinidine and 3-hydroxyquinidine based upon measurements of total and unbound serum concentrations were determined after a single dose (400 mg) and at steady state (200 mg every 6 h). 2. The oral clearance (7.6 +/- 1.9 vs 4.8 +/- 2.0 ml min-1 kg-1; P less than 0.05) and renal clearance (1.2 +/- 0.3 vs 0.63 +/- 0.25 ml min-1 kg-1; P less than 0.005) or quinidine were lower during steady state than after the single dose. 3. The area under the serum concentration vs time curve (AUC) of 3-hydroxyquinidine was greater at steady state than after the single dose (2.0 +/- 0.7 vs 3.0 +/- 0.6 mg l-1 h; P less than 0.05) and its renal clearance was less (3.0 +/- 1.1 vs 1.54 +/- 0.38 ml min-1 kg-1; P less than 0.05). 4. The slope of the relationship between quinidine concentration and change in QTc interval was greater at steady state (40.1 +/- 21.7 vs 72.2 +/- 41.7 ms/(mg l-1); P less than 0.05).     

克林沙星在大鼠体内的药代动力学和生物利用度

目的　研究克林沙星在大鼠体内的药动学和生物利用度。方法　HPLC法测定大鼠ig和iv克林沙星后的血药浓度,计算药动学参数和生物利用度。色谱柱为C₁₈柱(5μm),流动相为乙腈-0.05mol·L^-1柠檬酸三乙胺液(pH2.5)(20∶80),流速为1.0mL·min^-1,检测波长300nm。结果　克林沙星0.1-20μg·mL^-1呈良好线性关系,在大鼠体内的药动学过程符合一室模型,大鼠ig50和100mg·kg^-1后,C_max和AUC均与剂量呈正比,T_1/2与剂量无关;绝对生物利用度(F)为42%。结论　克林沙星50-100mg·kg^-1的吸收和消除呈一级动力学特征,在大鼠体内的生物利用度低。     

Pharmacokinetics of 2',3'-dideoxycytidine in rats: application to interspecies scale-up

The effects of dose on the pharmacokinetics of 2',3'-dideoxycytidine (DDC), a potent inhibitor of HIV replication, have been studied in rats. DDC was administered intravenously at doses of 10, 50, 100 and 200 mg kg-1. Plasma and urine drug concentrations were determined by HPLC. Non-compartmental pharmacokinetic parameters were calculated by area/moment analysis. DDC plasma concentrations declined rapidly with a terminal half-life of 0.98 +/- 0.18 h (mean +/- s.d.). No statistically significant differences were observed in pharmacokinetic parameters between the four doses. Total, renal and non-renal clearance values were independent of dose and averaged 1.67 +/- 0.24, 0.78 +/- 0.11, and 0.89 +/- 0.27 L h-1 kg-1, respectively. Approximately 50% of the dose was excreted unchanged in urine. Steady state volume of distribution was also independent of dose and averaged 1.2 +/- 0.21 L kg-1. Protein binding of DDC to rat serum proteins was independent of drug concentration with the fraction of drug bound averaging 0.45 +/- 0.12. Thus, the disposition pattern of DDC in the rat is independent of the administered dose even at high doses. Significant interspecies correlations were found for total, renal and non-renal clearance and steady state volume of distribution. Interspecies scaling resulted in superimposable plasma DDC concentration-time profiles from four laboratory animal species and man. Thus, plasma DDC concentrations in humans can be predicted from pharmacokinetic parameters obtained in laboratory animals.     

Evaluation of the anti-diabetic property of Morinda lucida leaves in streptozotocin-diabetic rats

The hypoglycaemic and anti-hyperglycaemic activities of a methanol extract of Morinda lucida Benth. (Rubiaceae) leaves were studied in normal and streptozotocin-diabetic rats. In normal rats, the extract demonstrated a significant (P < 0.05) and dose-dependent hypoglycaemic activity within 4 h after oral administration. The plasma glucose level of 400 mg kg(-1) of the extract at 4 h was 42.5 +/- 0.4 mg/100 mL (control 67.4 +/- 1.2 mg/100 mL). After 12 h, the plasma glucose level of rats administered 50, 100, 200 or 400 mg kg(-1) extract fell to 51.9 +/- 1.2, 47.3 +/- 0.8, 43.1 +/- 0.4 and 40.0 +/- 0.5 mg/100 mL, respectively. In hyperglycaemic rats, the extract produced a significant (P < 0.05) anti-diabetic effect from day 3 after oral administration, with 400 mg kg(-1) extract-treated animals having a plasma glucose level of 248.7 +/- 5.3 mg/100 mL compared with glibenclamide (10 mg kg(-1))-treated animals with a plasma glucose level of 251.5 +/- 5.8 mg/100 mL. These results suggest that the leaves of Morinda lucida have a strong glucose lowering property when administered to streptozotocin-treated rats.     

Species differences in the pharmacokinetics of recainam, a new anti-arrhythmic drug

The pharmacokinetics of recainam, an anti-arrhythmic drug, were compared in mice, rats, rabbits, dogs, rhesus monkeys, and man. Bioavailability was virtually complete in monkeys and dogs, 67 per cent in man and 51 per cent in rats. Non-linear kinetics between the oral and i.v. dose in rabbits precluded estimation of bioavailability. Linear plasma dose proportionality occurred in dogs between 6 and 60 mg kg-1 oral doses and rhesus monkeys between 1 and 15 mg kg-1 i.v. doses. A greater than proportional increase in the plasma AUC of recainam occurred between oral doses ranging from 54-208 mg kg-1 in mice, 25-110 mg kg-1 in rats, and 50-100 mg kg-1 in rabbits. In human subjects, the AUC/unit dose was linear between 400 and 800 mg. The terminal elimination t1/2 of recainam ranged from 1-5h in laboratory animals and man. The plasma Cmax and AUC of recainam were virtually identical after single or multiple (21 day) oral doses in dogs. After an i.v. dose, plasma clearance of recainam (l kg-1 .h) was 4.9-5.2 in rats and rabbits and 0.4-1.9 in dogs, rhesus monkeys, and man. The steady state volume of distribution was 2-5 times larger than the total body water of laboratory animals and man. Recainam was very poorly bound (10-45 per cent) to the serum proteins of rodents, rabbits, dogs, rhesus monkeys and man. In rhesus monkeys and man, recainam accounted for 10 per cent and 70 per cent, respectively, of the plasma radioactivity at 6 h post-dose. The pharmacokinetic profile of recainam in dogs most closely resembled that of man.     

Plasma concentrations and pharmacokinetics of midazolam during anaesthesia

Midazolam and 1-hydroxymidazolam plasma concentrations have been monitored and pharmacokinetic parameters of midazolam estimated during anaesthesia induced and maintained by its repeated injection according to two protocols (3 X 0.3 mg kg-1 at 45 min intervals or an induction dose of 0.3 mg kg-1 with maintenance doses of 0.15 mg kg-1 at 30 min intervals). Minimum plasma concentrations of midazolam measured just before each injection were 258.8 +/- 108.4 ng ml-1 for the first protocol and 353.1 +/- 55.2 ng ml-1 for the second protocol; maximum midazolam concentrations, measured 5 min after the last administration, were 1103.1 +/- 237.9 ng ml-1 and 743.0 +/- 103.2 ng ml-1, respectively, suggesting that a continuous infusion of midazolam after a loading dose should be better than repeated injections at keeping the concentration close to the sedative level of 400 ng ml-1. The estimated pharmacokinetic parameters were similar to those already published, except for the beta elimination half-life of midazolam (3.24 +/- 0.90 h for protocol 1 and 3.34 +/- 1.47 h for protocol 2) which was slightly longer than that reported for single dose studies. The comparison of plasma determinations, obtained either by gas-liquid chromatography or by a radioreceptor assay technique, clearly showed that 1-hydroxymidazolam, even after repeated midazolam administration, was not present at a concentration sufficient to affect the overall pharmacological activity of the parent drug.     

Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis.

Clinical assessment, plasma and synovial fluid kinetics were studied in 29 rheumatoid patients receiving 100 mg flurbiprofen twice daily. Clinical assessment and pharmacokinetic measurements varied widely within the group of patients. The average values for plasma clearance, volume of distribution and elimination halflife of flurbiprofen were 0.65 +/- 0.24 ml min-1 kg-1, 0.160 +/- 0.093 l kg-1 and 3.1 +/- 1.7 h, respectively. Synovial fluid drug concentrations peaked later and were lower than corresponding plasma concentrations: 5.2 h and 4.4 mg l-1 as against 1.49 h and 12.5 mg l-1, respectively. At 48 h after an oral dose of flurbiprofen, all the drug had been cleared from the synovial fluid. Synovial fluid drug concentrations were not related to synovial fluid albumin concentration or pH. There was a weak relationship between synovial fluid drug concentration and the thermographic measurements of disease activity. The fractions of flurbiprofen not bound to protein in synovial fluid and plasma were not significantly different. A simple model is proposed to account for the plasma and synovial fluid pharmacokinetics.     

Protective effect of Nigella sativa L.to gastric mucous of indomethacin-induced gastric ulcer rats

OBJECTIVE To investigate the effect of Nigella sativa L.as gastric protective on indomethacin-induced rats.METHODS the design of this research is randomized post test control group design.The rats were randomly divided into 5 groups which 5 rats in each.Rats were fasted for 8h before treatment.The first group was a control group(only gave aquadest as vehicle orally).The second group was subjected to induced with indomethacin 30mg·kg-1.The rest groups were subjected to induced by indomethacin and methanolic extract of Nigella sativa L.200,300 and 400mg·kg-1 every 8h for 24 h,respectively,for third,fourth and fifth group.Rats were sacrificed after anesthetized with ketamine and gastric were washed before observed.Macroscopic observation based on a score of lesion and microscopic observation on gastric based by histological HE staining.Whole data were analysis of an ANOVA statistical program.RESULTS The administration of Nigella sativa L.significantly decreased gastric ulcer macroscopically starting at dose 100,200 and 300mg·kg-1(P<0.05).Microscopic observation showed significant decreasing at dose 200 and 300mg·kg-1(P<0.05).Interestingly,there was no significant different between control and dose 300mg·kg-1.Negative correlation between lesion and doses were-0.919,-0.953 for macroscopic and microscopic lesion respectively.It means there was strong correlation between dose and lesion,higher dose lesser lesion.The mechanism of gastric protective of NigellasativaL.may caused by the bioactive compound such as thymoquinone which known as antiinflammation and antioxidant.CONCLUSION Methanolic extract of Nigella sativa L.decreased peptic ulcer both macroscopic and microscopic conditions on indomethacin-induced rats.