Determination of Loratadine in Human Plasma by High Performance Liquid Chromatography-Electrospray Mass Spectrometry and Studies on Its Pharmacokinetics and Relative Bioavailability

A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined by mass detector. The calibration curve of loratadine was linear within the range of 0.4～100 ng·mL -1 with r=0.9995 . The recovery of this method was within 95%～104%, within day and between day RSD were less than 12%. To study the pharmacokinetics and relative bioavailability of loratadine tablets, two formulations of loratadine tablets were given to 18 healthy male volunteers according to a randomized 2 way cross over design. The C max , AUC 0 t and T max values of the two formulations were 51.89±20.18 ng·mL -1 and 52.48±22.35 ng·mL -1 ; 140.75±88.42 ng·h·mL -1 and 147.24±92.33 ng·h·mL -1 ; 0.81±0.35 h and 0.81±0.27 h respectively. Results from statistic analysis showed that there were no significant difference between the C max , AUC 0-t and T max values of the two formulations. The relative bioavailability of tablets I with respect to tablets II was 97%±13% from the AUC 0 t measurement. Bioequivalance was observed between the two tablets.

Quantitative determination of D_(4)-cystine in mice using LC-MS/MS and its application to the assessment of pharmacokinetics and bioavailability

Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D_(4)-cystine was employed to generate calibration curves for the determination of levels of D_(4)-cystine and endogenous cystine in mice by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation assessments proved the sensitivity,specificity and reproducibility of the method with a lower limit of quantification(LLOQ)of 5 ng/mL over 5e5000 ng/mL in plasma.The pharmacokinetics of D_(4)-cystine were evaluated after administering injections and oral solutions,both of which minimally impacted endogenous cystine levels.The absolute bioavailability of cystine was 18.6%,15.1%and 25.6%at doses of 25,50 and 100 mg/kg,respectively.Intravenously injected D_(4)-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D_(4)-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain.

Study on the Pharmacokinetics and Relative Bioavailability of Irbesartan Capsules in Healthy Volunteers

The pharmacokinetics and relative bioavailability were studied in 18 healthy volunteers. A single oral dose of 150 mg irbesartan capsule (test) or tablet (reference) was given to each volunteer according to a randomized 2 way crossover study. The concentrations in plasma were determined by HPLC UV method. The main parameters of irbesartan capsules were: C max : 1.502±0.295 μg/ml, t max : 1.44±0.34 h, t 1/2 : 20.21±14.71 h, AUC 0 t : 11.087±3.443 μg/ml -1 ·h. The relative bioavailability of capsule to tablet was (101.4±28.9) %. The results of statistical analysis showed that two formulations were bioequivalent.

Enhancement in Bioavailability of CurCousin®, A Minor Metabolite from Curcuma longa by Addition of BioPerine® —A Pharmacokinetic Study

In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary modes of treatment. CurCousin® is a nutritional ingredient containing bioactive Calebin A, (analog of Curcumin) with self-affirmed GRAS status. CurCousin® has been a clinically studied dietary supplement ingredient with a positive impact on body weight, lipid levels and metabolic health. Bioenhancers play an important role in increasing the bioavailability of the active in turn enhancing efficacy as well as reducing the dosage required to achieve the therapeutic effect. This study investigated the possible pharmacokinetic interaction between CurCousin® at two different doses (2.25 and 4.5 mg/kg) in the presence and absence of BioPerine® (0.27 mg/kg), a natural bioenhancer in Sprague-Dawley rats. The results revealed that the addition of BioPerine® into CurCousin® (2.25 mg/kg) half the dose when administered enhances the bioavailability and was equipotent to CurCousin® (4.5 mg/kg) double the dose without BioPerine®. Thus, leading to future clinical studies to evaluate its improved pharmacological efficacy as well as reduced therapeutic dosage.

Pharmacokinetics and Relative Bioavailability ofsustained-release Tablets of Diclofenac Sodiumin Male Volunteers

The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.

Pharmacokinetics and Bioavailability of 2-Amino-6-Cyclopropylamino-9-(2,3 -Dideoxy-β-D-glyceropent-2-enofuranosyl) Purine (Cyclo-D4G) in Rats

AimTo characterize the pharmacokinetics of 2 -amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuran osyl) purine (Cyclo-D4G) following intravenous administration and oral administ ration to rats. MethodsThe concentrations of Cyclo-D4G in rat (Sprague-Dawley male rats) plasma and urine were analyzed by high performance liquid chromatography (HPLC). ResultsFollowing intravenous adm inistration to rats, concentrations of Cyclo-D4G in plasma declined with a term inal phase half-life of 0 78±0 14 h (±s). Total clearance was 0 90±0 21 L·h -1 ·kg -1 . Renal excretion of unchanged Cyclo-D4G accounted for approximately 20% of total clearance. Steady state volume of distr ibution was 0 91±0 07 L·kg -1 . After oral administration to rats, conce ntrations of Cyclo-D4G in plasma declined with a terminal phase half-life of 0 83±0 13 h (±s). Total clearance was 3 81±2 03 L·h -1 ·kg -1 . Renal excretion of unchanged Cyclo-D4G accounted for approximat ely 9% of total clearance. Oral bioavailability of Cyclo-D4G in rat was 26 9%. ConclusionThe favorable pharmacokinetic profiles and lower to xicity provide support for further development of Cyclo-D4G clinical trials.

Determination of Lovastatin Level in Human Plasma and Lovastatin Capsules Bioavailability in Healthy Volunteers Using HPLC-MS

Aim To establish a sensitive and specific liquid chromatography-mass spectrometry (HPLC-MS) method for measuring lovastatin level in human plasma and the relative bioavailability. Methods Lovastatin in the plasma was extracted with acetoacetate. Simvastatin was added as internal standard (IS). Samples were separated on a C_ 18 column with a mobile phase consisting of methanol and 50 mmol·L~ -1 sodium acetate (88 ∶ 12). The flow rate was 1 mL·min~ -1 . Sample was detected using an electrospray ionization (ES...

HPLC Determination of Captopril in Human Plasma with Pre-column Derivation and Solid-phase Extraction and Studies on Its Pharmacokinetic and Relative Bioavailability

A new pre-column derivation HPLC method with solid-phase extraction to determine captopril in human plasma was established. Derivation products were extracted by a solid-phase extraction method after the reagent, p-a-dibromoacetophenone(p-BPB), was added in the plasma samples. The samples were analyzed in a VP-ODS column with UV-detector. The calibration curve of captopril was linear within the range of 5~1000 ngmL-1 with r=0.9987, the recovery of this method was 98.652.04%, within day and between day RSD were no more than 3.4% and 8.4% respectively. To study the pharmacokinetics and the relative bioavailability of captopril tablets, two formulations of captopril tablets were given to 18 healthy male volunteers according to a randomized 2-way cross-over design with a 1-week washout period. The respective AUC0~6 , Cmax and Tmax values of the two formulations were 424.5125.7 and 439.4113.3 mghL-1; 505.9244.6 and 504.8172.2 mgL-1; 0.6620.181 and 0.5280.176 h. Results from statistics analysis showed that there were no significant difference between the AUC0~6 , Cmax and Tmax values of the two formulations, The relative bioavailability of tablets I with respect to II was 96.114.6% from AUC0~6 measurement. Bioequivalance was observed between the two tablets.

Pharmacokinetic Study of Ipriflavone in Healthy Volunteers by HPLC and Determination of the Relative Bioavailability of Its Tablet Preparation

Two kinds of Ipriflavone tablets (IP) were orally cross administered to 8 healthy volunteers. The serum level of IP at different time was determined by HPLC, 3P87 pharmacokinetic package was used in the analysis of the time course of serum concentration and it had shown that the data well fitted a 2 compartment model. Pharmacokinetic parameters and area under curve (AUC) were calculated. The relative bioavailability of Tabellae IP made in China vs that made in Japan (as a reference) was 1.003( P >0.05). The values of AUC T max and C max of the two preparations were also comparable by the statistical analysis, so they were bioequivalent.

Role of kaempferol to increase bioavailability and pharmacokinetics of nifedipine in rats

Herein,the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats.The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats.Moreover,the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats.The in vitro studies of kaempferol were investigated on P-glycoprotein(P-gp)and cytochrome P450(CYP)3A4 activity.Kaempferol reduced a 50%inhibitory concentration(IC50)of 8.6μmol·L-1 on CYP3A4 enzyme activity.Moreover,kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp.Depending on increased concentrations of kaempferol,the areas under the plasma concentration–time curve(AUC0-∞)and the peak concentration(Cmax)of nifedipine were increased after oral and intravenous administration.Moreover,the absolute bioavailability(AB)and relative bioavailability(RB)of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration.Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver,or both.

Advance in Pre-Clinical Pharmacokinetics of Paeoniflorin, a Major Monoterpene Glucoside from the Root of <i>Paeonia lactiflora</i>

Paeoniflorin (PF) is one of the main bioactive components of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora Pall. TGP exhibit various biological activities such as improvement in memory, hepatoprotection, antimutagenic properties and platelet aggregation inhibition. The aim of this paper is to review the pharmacokinetics (PK) of PF as a pure compound and in single or multiple herb(s) of traditional Chinese medicine (TCM) prescriptions. The distribution of PF or PF in TCM fitted one or two compartmental model after oral administration or intravenous injection, respectively. However, PF has a low bioavailability (BA) in rabbit (7.24%) and rat (3.24%) after oral administration. The PK profiles and BA of PF were remarkably improved when co-administered with sinomenine or glycyrrhizin acid. The PK profiles and BA of PF in Radix Paeonia Rubra (RP-R) and Jing-zhi guan-xin were improved, but in co-administration of RP-R with Radix Angelicae Sinensis, the BA was significantly reduced. PK profiles and BA of PF in Shan yao gan-cao tang or Danggui-Shaoyao-San was either remarkably improved or not. However, neither the PK profiles nor the BA of PF in Radix paeonia alba, Huangqin-tang Si ni san or Tang-Min-Ling-Wan was improved. Metabolism in the liver did not play any role in the low oral BA of PF. The low BA was thus attributed to poor permeation due to low lipophilicity, P-glycoprotein mediated efflux, intestinal bacteria and hydrolytic degradation in the intestine by the intestinal brush border lactase phlorizin hydrolase (LPH) and certain esterases. These findings show the in vivo course of PF and provide information on the maximum biological actions of PF that may help traditional Chinese herbal medicinal practitioners.

Determination of Mirtazapine in Human Plasma by HPLC-MS and Bioavailability of Newly Developed Mirtazapine Tablets in Healthy Volunteers

Aim To establish a sensitive and specific liquid chromatography-mass spectrometry method for determination of mirtazapine in human plasma and evaluation of its relative bioavailability. Methods After being alkalized by 25% ammonia, mirtazapine in the plasma was extracted with n-hexane. Desloratadine was used as internal standard (IS). Solu-tes were separated on a C_(18) column with a mobile phase of methanol-ammonium acetate buffer (pH 3.5) (75∶25). The flow rate of the mobile phase was 1 mL·min^(-1). Detection was performed on an electrospray ionization (ESI) mass spectrometer and operated in selected ion monitoring (SIM) and positive-ionization mode using target ionsat m/z 266.2 for mirtazapine and m/z 311.2 for the IS. The fragmentor voltage was 90 V. A randomized cross-over study was performed in 20 healthy volunteers. In the two study periods, twenty healthy Chinese male subjects received a single oral dose of mirtazapine 30 mg. Results The calibration curve was linear over the range of 0.3-200 ng·mL^(-1). The limit of quantitation was 0.1 ng·mL^(-1). The parameters for mirtazapine test tablet and reference tablet were as follows: T_(1/2)(24.7±4.1) and (23.6±4.3) h, T_(max)(1.6±0.8) and (1.5±0.8) h, C_(max)(95.9±29.8) and (91.9±26.7) ng·mL^(-1), respectively. Conclusion The established HPLC-MS method is rapid, sensitive and specific for the determination of mirtazapine in human plasma. The relative bioavailability was 100.0%±10.8%.

Absolute bioavailability,dose proportionality,and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method

Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.

A Comparative Study on Pharmacokinetics of Tricin, a Flavone from Gramineous Plants with Antiviral Activity

Tricin (and tricin containing plant extracts) has been shown to exert a pronounced antiviral activity, high radical scavenging activity and is favored for its safety profile. In the present study we have analyzed the pharmacokinetics of tricin after a single intravenous and oral administration to Wistar rats of an ethanol extract of Calamagrostis Adans and Deschampsia Beauv plants (test agent) at different doses. Tricin concentrations in blood plasma and blood cells were measured at different time points. Two-compartment (for intravenous injection) and one compartment (for oral administration) models were used for the analysis of tricin pharmacokinetics. The results showed that the pharmacokinetics of tricin after intravenous injection of test agent has a pronounced biphasic character, is well described by a two-compartment pharmacokinetic model, and is characterized by non-linear dose-dependence. The pharmacokinetics of tricin administered orally is characterized by a high rate of absorption from the gastrointestinal tract into the blood and rather slow elimination, which leads to a large volume of distribution in the body and a fairly high bioavailability. The obtained results indicate the advantages of the oral route of administration over the intravenous route.

Microdialysis in awake macaque monkeys for central nervous system pharmacokinetics

Background: The brain bioavailability of novel small molecules developed to address central nervous system disease is classically documented through ex vivo or in vivo analyses conducted in rodent models. Data acquired in rodent models are, however,not easily transferrable to human as the pharmacokinetic and pharmacodynamics profiles of the species are quite different.Methods: Using drugs selected for their differential transport across the blood-brain barrier, we here demonstrate the feasibility of brain microdialysis in normal vigil macaque monkey by measuring brain extracellular fluid bioavailability of carbamazepine, digoxin, oxycodone, and quinidine.Results: All drugs, but digoxin, were found in dialysate samples. Drugs that are substrate of P-glycoprotein show a difference of bioavailability or brain pharmacokinetic parameters between rodents and primates.Conclusion: Data suggest that brain microdialysis in vigil macaque monkey, the species of choice for classic pharmacokinetic/pharmacodynamics studies could help predicting human brain bioavailability of a small molecule depending on the protein involved in the efflux transport from the brain.

Quantification of neomangiferin in rat plasma by liquid chromatography–tandem mass spectrometry and its application to bioavailability study

Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC–MS/MS) method for the quantification of neomangiferin in rat plasma was developed. Using chloramphenicol as an internal standard(IS), plasma samples were subjected to a direct protein precipitation process using methanol(containing 0.05% formic acid). Quantification was performed by multiple reactions monitoring(MRM) method, with the transitions of the parent ions to the product ions of m/z 583.1-330.9 for NG and m/z 321.1-151.9 for IS. The assay was shown to be linear over the range of 0.2–400 ng/m L, with a lower limit of quantification of 0.2 ng/m L. Mean recovery of neomangiferin in plasma was in the range of 97.76%–101.94%. Relative standard deviations(RSDs) of intra-day and inter-day precision were both o 10%. The accuracy of the method ranged from94.20% to 108.72%. This method was successfully applied to pharmacokinetic study of neomangiferin after intravenous(2 mg/kg) and intragastric(10 mg/kg) administration for the first time. The oral absolute bioavailability of neomangiferin was estimated to be 0.53% 7 0.08% with an elimination half-life(t_(1/2)) value of 2.747 0.92 h, indicating its poor absorption and/or strong metabolism in vivo.

Validated,Rapid and Sensitive HPLC-MS/MS Method for Determination of 7,4'-Dihydroxylflavone in Rat Plasma and Its Application to Preliminary Pharmacokinetics

A sensitive,specific and rapid high-performance liquid chromatography-electronic spray ionization-tandem mass spectrometric method was developed and validated for the determination of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma.Genistein(internal standard,IS)was added in the collected plasma samples and subsided together by a simple one-step protein precipitation using acetonitrile-methanol(1:1,v/v).Chromatographic separation was performed on an Agilent Zorbax XDB C18 chromatography column and gradient elution with the mobile phase consisting of methanol and 0.1%formic acid was used.The mass spectrometric detection was performed by negative ion electro-spray ionization in multiple selected reactions monitoring(MRM)mode,with the transitions of m/z 253.1→113.0 for 7,4'-DHF and m/z 268.9→158.8 for IS.The calibration curve has liner relationship over the concentration range of 0.1-50.ng/mL(r=0.995.4).The intra-and inter-day precision(RSD%)was less than 10%,and the accuracy(RE%,relative error)ranged from-5.2%to 8.0%.The fully validated method was applied to the pharmacokinetics(PK)of 7,4'-dihydroxylflavone(7,4'-DHF)in rat plasma after oral administration(two doses:15 and 30.mg/kg)and intravenous injection(5.mg/kg).The result showed that Tmax and Cmax was 1.33±0.29.h and 0.12±0.02.ng/mL(15.mg/kg),and 1.17±0.29.h and 0.17±0.04.ng/mL(30.mg/kg),respectively.The bioavailability was 0.078%(15.mg/kg)and 0.070%(30.mg/kg),respectively.

Evaluation of Chito-Oligosaccharide(COS)in Vitro and in Vivo:Permeability Characterization in Caco-2 Cells Monolayer and Pharmacokinetics Properties in Rats

Chito-oligosaccharide(COS)had shown a variety of biological activities and potential biomedical implications.The present study investigated the pharmacokinetics,bioavailability,and in vitro absorption of COS with degrees of polymerization(DPs)2-7 and explored the influence of DPs on them.From Caco-2 cell permeation studies,COS were low permeability compounds with no directional effects,suggesting a low in vivo absorption mediated by facilitation diffusion and paracellular absorption.After an intragastrical administration to rats,COS2 showed the highest systemic exposure in six oligosaccharides.The bioavailability of COS2-7 was 7.33%,6.11%,4.67%,4.13%,4.02%,0.99%,respectively.Differences in bioavailability for each COS correlated to structural variations,with high DPs contributing to a decrease in bioavailability.In conclusion,COS could be absorbed by the intestinal tract both in vitro and in vivo.The very low oral bioavailability of COS could be due to low permeability.DPs can affect absorption and bioavailability of COS2-7.This study provided evidence for the absorption characteristics of COS2-7 to help us better understanding the pharmacological actions.

Pharmacokinetic Study of Nanoparticulate Curcumin: Oral Formulation for Enhanced Bioavailability

Curcumin, a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of Curcumin in inflammatory disorders, cardiovascular disease, cancer, Alzheimer’s disease and neurological disorders have been shown. However, the clinical application of Curcumin is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based drug delivery systems for Curcumin including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanoemulsions, complexes and dendrimer/dimer, have been attempted to enhance the oral bioavailability, biological activity or tissue-targeting ability of Curcumin. We attempted the nanosuspensions based delivery of curcumin. Nanonisation renders curcumin completely dispersible in aqueous media. To enhance the curcumin absorption by oral administration, nanoparticulate solid oral formulation of curcumin was prepared by us and the resulting capsule was then examined for its efficiency on bioavailability in Male Wistar rats at a dose of 100 mg curcumin/kg body weight and the pharmacokinetic parameters were compared to those of normal curcumin powder and a commercial curcumin capsule CUR-500. The bio-distribution of curcumin in organs of rat was also studied. Nanoparticulation significantly raised the curcumin concentration in selective organs in the body. The results obtained provide promising results for nanoparticulate Curcumin to improve its biological activities. Enhanced bioavailability of curcumin in the form of nanoparticle is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease. The available information also strongly suggests that nano-formulation of ingredients such as curcumin may be used as a novel nutrient delivery system too.

Bioavailability and pharmacokinetics of alantolactone from Inula helenium in rats following intravenous and oral administrations

Alantolactone, as the principal constituent oflnula Helenium L, has been shown various pharmacologic activities, such as anti-inflammatory and deworming. In the present study, we developed a high performance liquid chromatography （HPLC） method for the determination of alantolactone in rat plasma, and pharmacokinetics of alantolactone was investigated after intravenous and oral administrations to Wistar rats. Separation was achieved on C18 column （4.6 mm×250 mm, 5.0 μm） using a mobile phase consisting of methanol-water （70：30, v/v） at a flow rate of 1.0 mL/min. The wavelength of the ultraviolet detector was set at 239 nm. The excellent linearity was found over a concentration range of 0.08-10 μg/mL （R2 = 0.9998）. The intra- and inter-day precisions were good, and the RSD was lower than 2.27%. The mean absolute recovery of alantolactone in plasma ranged from 88.09% to 95.57%. After intravenous administration, alantolactone showed rapid systemic clearance （CL （0.11±0.014） L/h/kg） and small volume of distribution （Vd （0.71±0.14） L/kg）. The biological half life （t1/2） was 56.24 min. After oral administration, alantolactone showed rapid oral absorption in rats, with a short Tmax of （45.02±0.88） and （45.13±0.39） min for 14 and 28 mg/kg, respectively. The bioavailability of alantolactone in rats was 50.88%, indicating that alantolactone was orally available.