The pharmacokinetics and oral bioavailability studies of columbianetin in rats after oral and intravenous administration

Ethnopharmacological relevance

The roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan (RAP) has been used as Traditional Chinese medicine to treat rheumatic disease in China since ancient times, but its action mechanisms was not well understood. Columbianetin is one of the main active constituents isolated from RAP, which has been shown to have various biological activities, but the absorption characteristics and oral bioavailability dose proportionality of columbianetin in vivo were not studied.

Materials and methods

Male Sprague Dawley rats (210–230 g) received either an intravenous (i.v. 5, 10 and 20 mg kg⁻¹) or oral (5, 10 and 20 mg kg⁻¹) dose of columbianetin. The levels of columbianetin in plasma were measured by a simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) method. The simple liquid–liquid extraction with ethyl acetate was used for sample preparation. Osthole was selected as internal standard (IS).

Results

The chromatographic separation was accomplished on a C₁₈ column at a flow rate of 1 mL min⁻¹, where water–methanol was used as mobile phase. The calibration curve of the method was linear in the concentration range of 0.05–2000 μg mL⁻¹. The intra and inter-day accuracy for columbianetin in rat plasma samples were within 8% and the variation was less than 8.3%. This method was suitable for the determination and pharmacokinetic study of columbianetin in rat plasma after both intravenous and oral administration. The results indicated that maximum plasma concentrations(C_max) for the columbianetin (17–42 μg mL⁻¹) were achieved at 0.3–0.5 h post-oral dosing and the apparent volume of distribution (V/F) ranged from 0.38 to 0.44 L. Absolute bioavailability of columbianetin was assessed to be 81.13±45.85, 81.09±33.63 and 54.30±23.19%, respectively. Terminal elimination half-life (T_1/2) of the columbianetin after oral dosing was 60–90 min and were 2.5–3.3 fold longer than those observed for the i.v. dosing.

Conclusions

The pharmacokinetic properties of columbianetin in rat after oral administration were characterized as rapid oral absorption, quick clearance and good absolute bioavailability. The bioavailability of columbianetin ranged from 54 to 81% for 5, 10 and 20 mg kg⁻¹ oral doses. The bioavailability of columbianetin is independent of the doses studied. Columbianetin showed dose proportionality over the dose range 5–20 mg kg⁻¹. The results clearly demonstrated that columbianetin was one of the material bases of RAP. Furthermore, an HPLC method was demonstrated in this study for the research of traditional Chinese medicine.     

Comparative pharmacokinetic study of paeoniflorin after oral administration of decoction of Radix Paeoniae Rubra and Radix Paeoniae Alba in rats

An investigation was designed and conducted to compare the pharmacokinetics difference of paeoniflorin after oral administration of the extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba to rats on separate occasions. Quantification of paeoniflorin in rat plasma was achieved using a simple and rapid HPLC method for pharmacokinetic study. After oral administration of decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba, paeoniflorin was absorbed and reached a maximum concentration of 3.69 ± 1.46 and 1.46 ± 0.29 (p < 0.05) μg/ml at 1.67 ± 0.43 and 0.80 ± 0.35 h (p < 0.05), respectively. Compared to the AUC (18.85 ± 7.54 μg h/ml) after oral administration of the paeoniflorin solution, a smaller AUC (10.61 ± 1.51 μg h/ml, p < 0.05) and a larger AUC (24.89 ± 7.41 μg h/ml) of paeoniflorin after oral administration of the decoctions of Radix Paeoniae Alba and Radix Paeoniae Rubra were obtained, respectively. There were statistically significant differences in pharmacokinetic parameters of paeoniflorin including the t_max, C_max, AUC, t_1/2, CL, and V_d among the animals orally administered the decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba. In particular, the parameters of t_max, C_max, and AUC of paeoniflorin were remarkably increased (P < 0.05, P < 0.001) when oral administering paeoniflorin in the decoctions of Radix Paeoniae Rubra, but t_1/2, V_d, and CL were decreased (P < 0.05 or P < 0.01), in comparison of the decoction of Radix Paeoniae Alba.     

Gender-dependent pharmacokinetics of lignans in rats after single and multiple oral administration of Schisandra chinensis extract

Ethnopharmacological relevance

Schisandra chinensis (S. chinensis), a traditional Chinese medicine, has been widely used as sedatives and tonics in clinic. Schisandra lignans are believed to be the major bioactive components in S. chinensis. However, there is a lack of information about the effects of gender and repeated-dose on the pharmacokinetic properties of the schisandra lignans.

Aim of the study

The study was performed to investigate the influence of gender on the pharmacokinetics of schisandra lignans after administration of S. chinensis extract and to compare their pharmacokinetic behaviors between single and multiple administration.

Materials and methods

Two groups of rats (half male and half female) were received a single dose or multiple doses of S. chinensis extract, respectively. A liquid chromatography–tandem mass spectrometry method was developed and validated to determine the plasma concentrations of schisandra lignans.

Results

The pharmacokinetic parameters of schisandrin, schisandrol B, deoxyschisandrin, γ-schisandrin and schisantherin A were significantly different by gender difference. The t_1/2 of all the tested schisandra lignans in female rats were 2–9 times longer than the corresponding values in male rats. The C_max and AUC_0−t of these schisandra lignans except schisantherin A in female rats were 5–50 times higher than those in male rats. The pharmacokinetic profiles of schisandrin, schisandrol B, deoxyschisandrin and schisantherin A in both gender rats after multiple doses were similar to the corresponding profile after single dose.

Conclusion

All the tested schisandra lignans showed slower elimination and higher bioavailability in female rats after single or multiple administration of S. chinensis extract compared with male rats. Their pharmacokinetic profiles were not affected by repeated-dose except γ-schisandrin, which was eliminated more slowly in female rats after multiple administration.     

Pharmacokinetic comparisons of typical constituents in white peony root and sulfur fumigated white peony root after oral administration to mice

Aim

White peony root and sulfur fumigated white peony root are produced by different processing methods from the root of Paeonia lactiflora Pall, but the two traditional Chinese medicines are used under the same common name white peony root. In order to clarify the influence of sulfur fumigation on pharmacokinetics of the main monoterpene glucoside components in white peony root, an investigation was carried out to compare the pharmacokinetics of sodium paeoniflorin sulfonate (1) and paeoniflorin (2), benzoylpaeoniflorin sulfonate (3) and benzoylpaeoniflorin (4), as well as 1 in sulfur fumigated white peony root extract (SWPE) and 2 in white peony root extract (WPE).

Materials and methods

A high-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of the four analytes. Kunming species of mice were orally administered the four compounds and the two extracts with approximately the same dose.

Results

It was found that C_max and AUC of 1 and 3 were increased (P < 0.05), and the T_max and t_1/2 were prolonged (P < 0.05) by comparison with that of 2. Similar results were also observed for the pharmacokinetics parameters of 1 in SWPE and 2 in WPE. However, benzoylpaeoniflorin (4) was not detected in plasma collected at certain intervals after administered orally to mice.

Conclusions

These results indicate that sulfonation of the monoterpene components could improve the bioavailability and delay the absorption of them in mice.     

Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats

Ethnopharmacological relevance

Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and antitumor effects, celastrol has been considered as a promising candidate for drug development.

Aim of the study

To establish a sensitive LC–MS/MS method to investigate the pharmacokinetic properties of celastrol in rats. Key pharmacokinetic issues of celastrol including oral bioavailability, comparative pharmacokinetics between pure compound and tablet preparation, as well as gender-related pharmacokinetic difference are to be addressed for the first time.

Materials and methods

Sprague–Dawley rats were administrated an intravenous dose (100 μg kg⁻¹) of pure celastrol and an oral dose (1000 μg kg⁻¹) of pure celastrol and TGV tablets (corresponding to 534 μg kg⁻¹ of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration–time curve (AUC), maximal plasma concentration (Cmax), the time for maximal concentration (Tmax) and mean residence time (MRT) were estimated by Drug and Statistic1.0 pharmacokinetic software (Chinese Pharmacological Association, Anhui, PR China). Statistical analysis was performed using two one-side t test with p-values less than 0.05 as the level of significance.

Results

The standard curve of celastrol showed good linearity in the concentration range of 0.11∼54.3 ng mL⁻¹ in our current method, with acceptable selectivity, precision, recovery, and stability. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41) μg L⁻¹ and (379.49±118.19) μg h L⁻¹, which were significantly higher (p<0.01) than that in males with the values of (14.31±7.33) μg L⁻¹ and (188.17±92.33) μg h L⁻¹.

Conclusion

Celastrol administered orally in the rat was poorly absorbed into the systemic circulation. However, the poor absorption of celastrol could be greatly improved when celastrol-containing TGV tablets orally administered, and thereby the oral bioavailability of celastrol was significantly increased. As for gender difference, female rats showed significantly better absorption of celastrol than males.     

芍药苷对大鼠急性放射性肝损伤的保护作用

目的：探讨芍药苷（paeoniflorin,PAE）对大鼠急性放射性肝损伤（acute radiactive hepatic injury,ARHI）的保护作用。方法按随即区组法将SD雄性大鼠随机分为正常对照组,模型对照组,芍药苷小剂量组（20mg/kg）、中剂量组（40 mg/kg）、大剂量组（80 mg/kg）,赤苷组（50 mg/kg）。除正常对照组外,其余各组大鼠均采用VARIN 21-EX直线加速器照射右半肝,其中芍药苷组和赤苷组在照射后每天给予对应剂量药物灌胃,正常对照组、模型对照组给予等容积生理盐水灌胃,各组大鼠在第2、4周末分批取材,取动脉血离心和大鼠右半肝标本10%福尔马林溶液固定备用。分别测定大鼠血清天冬氨酸转氨酶（AST）、谷氨酸转氨酶（ALT）,肝组织中谷胱甘肽（GSH）、过氧化物歧化酶（SOD）含量及HE病理染色评分。结果模型对照组于第2周末肝组织HE病理染色评分（2.25±0.53）分升高,AST、ALT分别为（112.83±19.20）U/L、（80.00±21.97）U/L,与正常对照组（63.06±7.15）U/L、（42.30±4.45）U/L比较明显升高（P＜0.01）。芍药苷小、中、大剂量组第2周末肝脏GSH含量分别为（60.89±8.43）U/mg、（67.84±9.05）U/mg、（71.92±8.11）U/mg,肝脏SOD含量分别为（118.45±11.98）U/mg、（120.49±13.49）U/mg、（129.65±13.89）U/mg,高于模型对照组（37.32±11.25）U/mg、（90.54±12.12）U/mg,（P＜0.05或0.01）。结论受照大鼠在第2周开始出现急性肝损伤,芍药苷对急性放射性肝损伤大鼠有保护作用。     

Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone,Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid

Ethnopharmacological relevance

Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China.

Materials and methods

An LC–MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20 mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test.

Results

The results showed that the pharmacokinetic parameters C_max, AUC_0–∞, V_z/F and CL_z/F were significantly different (P<0.05) among the three types of swertiamarin administration.

Conclusions

The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats.     

当归四逆汤中肉桂酸及甘草酸在大鼠血清中含量测定及药动学研究

目的:测定大鼠灌胃当归四逆汤后血清中肉桂酸、甘草酸血药浓度及药代动力学参数。方法:利用高效液相色谱(HPLC)法测定大鼠血清中肉桂酸、甘草酸血药浓度,应用3P97软件计算药代动力学参数。结果:大鼠口服当归四逆汤后肉桂酸药代动力学参数为Cmax9.2008(mg/L),AUC 304.0734(mg/L).min,甘草酸药代动力学参数为Cmax51.1330(mg/L),AUC 21476.9688(mg/L).min。结论:大鼠口服当归四逆汤后肉桂酸吸收快,代谢也较快;而甘草酸吸收快,但代谢相对较慢。     

大鼠体内泻心汤蒽醌类成分尿排泄动力学研究

目的:研究泻心汤(大黄、黄连、黄芩)中蒽醌类成分在大鼠体内尿排泄动力学规律.方法:建立大鼠尿中芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚高效液相色谱(HPLC-FLD)测定方法.大鼠灌胃给予泻心汤12 g/kg,药前及药后不同时间采集尿样,用HPLC-FLD法分析尿中蒽醌类成分,测定5种葸醌类成分经时变化,根据尿排泄量-时间数据计算排泄动力学参数.结果:大鼠灌胃给予泻心汤后,芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚均从肾脏经尿液排泄;排泄T1/2分别为:(3.46±1.18)h,(3.24±0.60)h,(4.69±1.99)h,(4.49±1.63)h,(5.65±1.74)h;48 h累积排泄量分别为:(11.28±4.30)μg,(116.73±17.46)μ斗g,(5.48 4-2.92)μg,(9.53±2.67)μg,(0.41±0.20)μg.结论:泻心汤中5种蒽醌类成分均可从尿中排泄,尿中排泄量占给药量均<10%.     

盐酸小檗碱对大鼠口服地高辛药动学的影响

目的:研究盐酸小檗碱(BBR)与地高辛(DIG)合用对大鼠体内DIG药动学的影响.方法:大鼠随机分为DIG单用组和DIG+BBR低、中、高剂量合用组.大鼠单剂量或多剂量给予BBR后,放免法测定单次口服DIG的血药浓度.药-时数据经3P97药动学软件处理,获得各组药动学参数.结果:合用后,BBR在低剂量时(10 mg·kg-1)对DIG的药动学过程无显著影响;但在中、高剂量(30,100 mg·kg-1)时有显著影响,AUC(0-1)分别增加了33%,70%(单剂量)和27%,75%(多剂量)(P<0.05).结论:体内研究表明BBR与DIG合用时,在一定浓度范围内,可明显提高其生物利用度,其机制可能与BBR抑制肠道P-糖蛋白有关.     

In vivo pharmacokinetics of bakuchiol after oral administration of bakuchiol extraction in rat plasma

Ethnopharmacological relevance

Psoralea corylifolia L. (Fabaceae) was a traditional Chinese medicine for the treatment of various skin diseases such as psoriasis, vitiligo and chronic graft-versus-host, and has been proved to show anticancer, cytotoxic, anti-bacterial, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac and tonic effects. Bakuchiol was one of the main active ingredients of this traditional Chinese medicine.

Aim of the study

In this paper, pharmacokinetic study was conducted to obtain pharmacokinetic parameters of bakuchiol.

Materials and methods

Bakuchiol was enriched using resin inform the ethanol extract of Psoralea corylifolia L., HPLC-UV was used to determine the concentration of bakuchiol in rat plasma at different time points after administration. The main pharmacokinetic parameters of bakuchiol in rat were obtained based on the analysis of the plasma sample.

Results

The pharmacokinetics of bakuchiol was fitted with a two-compartment model and it was eliminated relative slowly in rats.

Conclusions

The HPLC-UV method was successfully applied to study the pharmacokinetics of bakuchiol in rats.     

P-gp抑制的羟基喜树碱纳米混悬剂口服给药后在大鼠体内药动学的研究

目的:研究羟基喜树碱( HCPT)纳米混悬剂口服给药后在大鼠体内的药代动力学.方法:采用高效液相色谱,荧光检测法( HPLC-FD)测定HCPT的血药浓度,Diamonmsil-C18色谱柱(4.6 mm×200 mm,5 pun),流动相甲醇-0.3 qo冰醋酸(用三乙胺调pH 5.0)(57:43),流速1.O mL.min“;FP-920型JASCO荧光检测器,激发波长363 nm;发射波长550 nm;柱温35℃;进样量20 pL.用DAS 2.O药动学程序处理HCPT的血药浓度一时间数据.结果:本测定方法HCPT在l~50 Vg- L-I线性关系良好,最低定量限l懈.L“;日内、日间精密度均小于4.3%;高、中、低3个血药浓度的提取回收率分别为98.94%,95.88010.102.7%,符合体内药物分析的要求.HCPT在大鼠体内的药代动力学符合二室开放模型,Cm为13.10峭-L-l,Zr呲为0.75 h,Il/2a为8.242 h,tl佯为136.122 h,AUCo.,为116.77懈.h.L-1,AUCo..为161.93 Vg.h.L-1.结论:本研究中的HPLC-FD专属性强,重复性好,操怍简便,适合于研究HCPT在大鼠体内的药动学和药物浓度检测.本实验中的纳米混悬剂能加快HCPT口服吸收速度,为提高口服生物利用度提供了可能性.     

微透析法进行芎冰喷雾剂鼻腔给药的脑内药动学研究

目的:测定芎冰喷雾剂经鼻腔给药后主要成分磷酸川芎嗪(TMPP)在大鼠脑内的药代动力学参数。方法:大鼠鼻腔或静脉注射给予芎冰喷雾剂后,利用微透析技术进行脑内药动学研究,高效液相色谱法测定透析液样品中TMPP的浓度,用Das2.0药动学软件计算主要药动学参数。结果:鼻腔给药和静注给药后TMPP在脑内的吸收均符合一室模型,芎冰喷雾剂鼻腔给药与静注给药TMPP都迅速进入脑内达到峰浓度,鼻腔给药TMPP在脑内的停留时间更长。结论:微透析法能较好的反映芎冰喷雾剂鼻腔给药后TMPP的药动学特征,鼻腔给药是治疗缺血性脑血管机能不全急性期的一种速效途径。     

Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats

Ethnopharmacological relevance

Cimicifuga foetida L., a traditional Chinese medicine, has been used as an anti-inflammatory, antipyretic and analgesic remedy. The primary active constituents are believed to be present in the triterpene glycoside fraction.

Materials and methods

To develop an LC–MS/MS assay for four major cimicifugosides [cimicifugoside H-1 (Cim A), 23-epi-26-deoxyactein (Cim B), cimigenolxyloside (Cim C) and 25-O-acetylcimigenoside (Cim D)] obtained from C. foetida L. and apply it to investigate their pharmacokinetic (PK) properties and bioavailabilities through oral administration of C. foetida L. extract (12.5, 25 and 50 mg/kg) and single intravenous (i.v.) doses (5 mg/kg) of the individual cimicifugosides in rat. PK parameters were estimated by non-compartmental analysis.

Results

All calibration curves showed excellent linear regressions (all r>0.995) within the range of tested concentrations. The intra- and inter-day variations were <15% in terms of RSD. The molar ratio of Cims A, B, C, and D in the extract was 20.7:1.4:2.9:1. PK parameters for Cims A, B, C, and D following oral administration of the extract were respectively: C_max 4.05–17.69, 90.93–395.7, 407.1–1180 and 21.56–45.09 pmol/mL; T_max 0.46–1.28, 2.00–4.67, 14.67–19.67 and 8.08–14.27 h; absolute oral bioavailability (F) 1.86–6.97%, 26.8–48.5%, 238–319% and 32.9–48%. PK parameters after i.v. administration of individual cimicifugosides were respectively: elimination half-life 1.1, 2.5, 5.7 and 4.2 h; clearance 15.7, 0.48, 0.24 and 1.13 mL/h kg.

Conclusions

Systemic exposure to Cims B, C and D following oral administration of the extract was significantly greater than to Cim A despite the predominance of Cim A in the extract. Significantly different clearance and interconversion from Cim A to Cim C probably accounts for the different exposure to the four cimicifugosides.     

Comparative pharmacokinetics of baicalin and geniposide in juvenile and adult rats after oral administration of Qingkailing Granules

Objective: To explore the effect of age on Qingkailing Granules disposition by comparing the pharmacokinetics of geniposide and baicalin in juvenile and adult rats. Methods: A simple and rapid LC-MS/MS method was developed and validated to simultaneously determine geniposide and baicalin in rat plasma after a simple protein precipitation. The analytes were separated on an Agilent ZORBAX Extend-C18 column. The mobile phase consisted of acetonitrile and water with 0.1% (volume percent) formic acid at a flow rate of 0.6 mL/min. The ionization was conducted using an ESI source in negative ion mode. Multiple reaction monitoring was used for quantification at transitions of m/z 445.0 → m/z 268.9 for baicalin, m/z 433.2 → m/z 225.0 for geniposide, m/z 431.0 → m/z 341.0 for vitexin (IS). Juvenile and adult rats were administrated Qingkailing Granules (3 g/kg) orally. Plasma concentrations of baicalin and geniposide were determined by LC-MS/MS. Results: The linear ranges of the analytes were 1–1000 ng/mL for baicalin and 2–2000 ng/mL for geniposide. The method was successfully applied to compare the pharmacokinetics of the analytes between juvenile and adult rats after oral administration of Qingkailing Granules. AUC was bigger in adult rats, while t1/2 was longer in juvenile rats. Conclusion: These results suggested that the absorption and elimination of baicalin and geniposide in juvenile rats was lower than that in adult rats. Additional attention should be paid to the pharmacokinetic difference when Qingkailing Granules were used in children.     

LC-MS测定制吴茱萸提取物中吴茱萸碱、 吴茱萸次碱在大鼠体内的药动学

目的:建立LC-MS测定大鼠血浆中吴茱萸碱、吴茱萸次碱含量的方法,并探讨其在大鼠体内的药动学过程.方法:大鼠灌胃制吴茱萸提取物后不同时间点采血,LC-MS测定受试成分血药浓度,并用WinNonlin 5.1软件计算药动学参数.结果:吴茱萸碱、吴茱萸次碱分别在0.5 ～100 μg·L-1(r =0.995 9)和1～200 μg·L-1(r =0.999 3)线性关系良好,平均同收率均大于76％,日内、日间RSD均小于15％.大鼠灌胃制吴茱萸提取物0.4,0.8,2.4g· kg-1后,吴茱萸碱AUC分别为(2 215.24 ±414.49),(4 230.62±753.77),(13 219.21±3 740.95) min·ng-1.mL-1;t1/2分别为(146.57±38.38),(114.38±14.65),( 163.37±8.83) min; CL_F分别为(184 607.29±32 502.21),(192 878.22±31 897.37),( 193 224.63±62278.74) mL·min-1;吴茱萸次碱的AUC分别为(2 283.53±298.51),(4 424.84±276.95),(14 239.93±3 648.27) min·ng-1·mL-1;t1/2分别为(167.10±15.82),(131.58±20.07),(144.41±13.65) min;CL_F分别为(1 177 340.54±24942.21),(181 262.92±11 162.22),(177 508.10±52 611.80) mL· min-1.结论:本法专属性强,灵敏度高,可用于吴茱萸碱、吴茱萸次碱的体内定量分析.吴茱萸碱、吴茱萸次碱在大鼠体内符合一级吸收的一室模型.     

葛根提取物不同途径给药后葛根素在大鼠体内药代动力学研究

目的:研究葛根提取物经不同途径给药后葛根素在大鼠体内的药代动力学。方法:葛根提取物经大鼠尾静脉注射(i.v.)、鼻腔给药(i.n.)(20mg/kg)及灌胃给药(i.g.)(200mg/kg),以甲醇沉淀血浆蛋白质,反相高效高相液相色谱测定葛根素在大鼠血浆中的浓度,用Kinetica程序软件计算药代动力学参数。结果:葛根素在(0.05315-53.1500)mg/L线性关系良好(r=0.9999),回收率为95.72%,RSD=2.31%;计算出尾静脉注射给药途径主要药动学参数:AUC=(795.41±59.85)mg.L-1.min-1,Cmax=(65.74±7.71)μg/mL,MRT=(18.96±2.08)min,t1/2=(16.95±3.55)min;鼻腔给药途径主要药动学参数:AUC=(227.34±19.42)mg.L-1.min-1,Cmax=(3.78±1.80)μg/mL,Tmax=(7.50±2.74)min,MRT=(117.09±38.37)min,t1/2=(22.50±10.60)min;灌胃给药途径主要药动学参数:AUC=(732.48±471.57)mg.L-1.min-1,Cmax=(3.53±1.32)μg/mL,Tmax=(27.00±16.43)min,MRT=(394.22±209.24)min,t1/2=(237.84±112.39)min;结论:葛根提取物经3种途径给药的主要药动学参数具有显著性差异,鼻腔给药吸收迅速,生物利用度较口服高,该结果可以为葛根提取物的给药途径和剂型研究提供科学依据。