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@#The aim of this study was to investigate the in vivo pharmacokinetic behavior characteristics and in situ intestinal absorption characteristics of the evodiamine lipidic nanoparticle in rats. Evodiamine lipidic nanoparticle was prepared by the solvent evaporation methods. The particle size and zeta potential of evodiamine lipidic nanoparticle were measured by dynamic light scattering analysis. Male SD rats were divided into two groups randomly. Each group was given single dose of evodiamine and evodiamine lipidic nanoparticle by gavage at evodiamine dose of 250 mg/kg,respectively. The blood samples were collected at scheduled time points. The content of evodiamine in plasma samples was determined by high performance liquid chromatography (HPLC) method. The main pharmacokinetic parameters of evodiamine and evodiamine lipidic nanoparticle were calculated using DAS 2.1.1 software. Moreover,the single-pass intestinal perfusion model was also established in rats to investigate the in situ intestinal absorption characteristics of evodiamine lipidic nanoparticle. The mean particle size and mean zeta potential of evodiamine lipidic nanoparticle were 180.10 nm and -17.90 mV,respectively. The area under the curve of evodiamine and evodiamine lipidic nanoparticle were (862.60±14.03) and (4084.31±17.21) μg/L·h,respectively,and the peak concentration were (163.40±13.27) and (616.90±21.04) μg/L,respectively. Moreover,the absorption of evodiamine lipidic nanoparticle was significantly higher than that of evodiamine in each segment of intestinal tract in rats (P<0.05). The absorption of evodiamine lipidic nanoparticle in colon was better than those of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum and ileum. The absorption rate constant of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum,ileum and colon were (45.10±6.08)×10-5,(48.20±1.21)×10-5,(22.10±3.18)×10-5,(59.10±1.21)×10-5 and (90.00±3.85)×10-5 s-1,respectively,and the effective permeability coefficient in duodenum,jejunum,ileum and colon was (44.10±0.51)×10-5,(17.21±0.77)×10-5,(35.36±0.31)×10-5 and (40.33±0.34)×10-5 cm/s,respectively.All in all, evodiamine lipidic nanoparticle remarkably improved the in situ intestinal absorption of evodiamine in different segments of the intestinal tract in rats and its oral bioavailability in rats.
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Objective: To prepare glycyrrhizic acid (GL)-Pluronic F127 (F127)/polyethylene glycol 1000 vitamin E succinate (TPGS) mixed nanomicelles (MMs) and improve oral absorption of GL. Methods: GL-F127/TPGS-MMs was prepared by thin film dispersion method. The encapsulation efficiency and drug loading of MMs were used as evaluation indexes. The formulation and process, including the ratio of F127 to TPGS, the concentration of polymer and GL, hydration temperature and time, were optimized by the single factor experiment. The morphology of MMs was investigated by transmission electron microscopy. The single-pass perfusion model was established in rats to investigate the intestinal absorption characteristics of GL-F127/TPGS-MMs with absorption rate constant (Ka) and apparent absorption coefficient (Papp) as evaluation indexes. Results: The optimal formulation and process of GL-F127/TPGS-MMs were as follows: TPGS 180 mg, F127 270 mg, GL 70 mg, hydration temperature 50 ℃ and hydration time 3 h. The prepared GL-F127/TPGS-MMs had good clarity and the particle size, polydispersity index, and Zeta potential were (28.20 ± 5.63) nm, 0.20 ± 0.06, and (-5.24 ± 1.55) mV, respectively. The encapsulation efficiency and drug loading were (97.57 ± 5.29) % and (13.13 ± 0.71) %, respectively. The MMs were spherical with distinct vesicle structure. The absorption of GL in the jejunum segment was significantly higher than that in the ileum segment (P < 0.05). Compared with raw GL, GL-F127/TPGS-MMs had a statistically significant higher absorption rate in the intestinal segment (P < 0.05). Conclusion: The prepared GL-F127/TPGS-MMs could significantly improve the absorption of GL in vivo.
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Objective: To explore the effect of Acori Tatarinowii Rhizoma on intestinal absorption of ginsenosides in Dingzhi Xiaowan,and reveal the mechanism of Acori Tatarinowii Rhizoma acting as " adjuvant drug" in this formula. Method: The contents of ginsenoside Rg1,Re and Rb1 were measured by UPLC-MS/MS and the absorption of three ginsenosides in different intestine segments was investigated by rat single pass intestinal perfusion in situ,including absorption rate constant(Ka) and apparent permeability coefficient(Papp).Everted intestinal sac model was used to investigate the absorption dosage of three ginsenosides affected by volatile oil from Acori Tatarinowii Rhizoma and verapamil[Ver,a P-glycoprotein(P-gp) inhibitor]. Result:Papp values of three ginsenosides were ≤ 0.191×10-3 cm·min-1 in Dingzhi Xiaowan when lack of Acori Tatarinowii Rhizoma.Compared with lack of Acori Tatarinowii Rhizoma in Dingzhi Xiaowan group,the Ka and Papp values of lack of volatile oil from Acori Tatarinowii Rhizoma in Dingzhi Xiaowan group slightly increased without significant difference in the four intestinal segments,but when the prescription had Acori Tatarinowii Rhizoma,the Ka increased by 3.97-8.35 fold and the Papp increased by 3.99-8.49 fold.The results of everted intestinal sac test showed that volatile oil of Acori Tatarinowii Rhizoma could significantly promote the intestinal absorption of ginsenoside Rg1,Re and Rb1,but there was no dose-dependent. Conclusion:Volatile oil of Acori Tatarinowii Rhizoma can promote the intestinal absorption of three ginsenosides in Dingzhi Xiaowan,and the mechanism may be related to the inhibiting function on P-gp.
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Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.
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Humans , Biopharmaceutics , Intestinal Absorption , Intestines , Medicine, Chinese Traditional , Perfusion , PermeabilityABSTRACT
For the effects of multi-component environment on the solubility and permeability of single components,and the problems of biopharmaceutical attribute classification of single components in the compound prescriptions environment,baicalein was used as the research object in this study to investigate the biopharmaceutic attributes of single-component and their traditional Chinese medicine( TCM) biopharmaceutic attributes in the multi-component environment of Gegen Qilian Decoction. Shaking flask method,intrinsic dissolution rate test and HPLC were used to determine solubility of baicalein. Markers specified by FDA were utilized as permeable boundary reference materials to verify the applicability of the single-pass intestinal perfusion method( SPIP),and the quantitative research on the permeability of baicalein was also conducted. It is concluded that baicalein could be categorized as BCS-Ⅱ drug based on its low solubility and high intestinal permeability values,and it may be categorized into CMMBCS-I in the multi-component environment of Gegen Qilian Decoction due to its poor solubility but enhanced solubility and permeability in compound environment. This study could provide verification ideas for clinical determination of the best human oral dose of baicalein,and provide the data basis for the study of biopharmaceutics classification system of Chinese materia medica( CMMBCS).
Subject(s)
Humans , Biopharmaceutics , Classification , Drugs, Chinese Herbal , Chemistry , Flavanones , Chemistry , Intestinal Absorption , Materia Medica , Classification , Permeability , SolubilityABSTRACT
Objective To study the intestinal absorption kinetics of Tripterygium wilfordii (TW) solid dispersions and the effects of different intestinal segments, drug concentrations, pH value, and P-glycoprotein (P-gp) on intestinal absorption. Methods The absorption behavior was investigated in situ with a single-pass intestinal perfusion (SPIP) model in rats. The content of each index component was determined by HPLC. The gravimetric method was used to correct the data and calculate the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of each index component. Results The index components of TW were absorbed in the whole intestine, and the absorption rate constant (Ka) of all the index components of TW solid dispersion was significantly increased than that of extract (P < 0.05), and had some differences among different segments. With the increase of drug concentration, the absorption of each index component had saturation phenomenon, which indicated that it may be carrier-mediated transport mechanism. Acidic environment (pH 5.4) was beneficial to the absorption of various index components, especially the acidic content celastrol. After adding P-gp inhibitor, the Ka and Papp of celastrol were significantly different from those without P-gp inhibitor (P < 0.05), which suggested that it may be the P-gp substrate. Conclusion All the index components of TW solid dispersion are absorbed in the whole intestine and have saturation phenomenon, which suggested the absorption may be carrier-mediated transport mechanism. Acidic environment is beneficial to the absorption of all components. The absorption process of celastrol is affected by drug concentration and P-gp inhibitor, which indicated that it may be P-gp substrate. The preparation of solid dispersing can significantly enhance the absorption of various components of TW, suggesting that all the index components are BCS II drugs, and the bioavailability of the preparation may be improved.
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To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.
Subject(s)
Animals , Rats , Drugs, Chinese Herbal , Pharmacokinetics , Intestinal Absorption , Intestines , Phytochemicals , PharmacokineticsABSTRACT
The intestinal absorption properties of four main effective components(gallic acid, ocinolglucoside, ethyl gallate and penta-O-galloyl-β-D-glucose) in Rhus chinensis extracts were investigated by in situ single-pass intestinal perfusion model in rats. The liquid accumulation of perfusion was corrected by gravimetry. The HPLC method was established to determine the concentration of the four effective components in the intestinal perfusion. It showed significant differences(Pethyl gallate>gallic acid>ocinolglucoside, with significant differences between them(P<0.05). In conclusion, gallic acid, orpheolglucoside, ethyl gallate and pentacyl-glucose could be absorbed in the whole intestine. Their absorption rate and permeation ability were related to the intestinal section and the perfusate concentration. These results indicated potential active transport or facilitated diffusion in the intestinal transport process of the four effective components.
Subject(s)
Animals , Rats , Chromatography, High Pressure Liquid , Hydroxybenzoates , Metabolism , Intestinal Absorption , Perfusion , Phytochemicals , Metabolism , Rhus , ChemistryABSTRACT
Intestinal permeability is one of key factors determing absorption of oral drug products. It is a big challenge to assess permeability of compounds with high accuracy and high efficacy during research and development process. In this review, the principles, strengths, weaknesses and advances of common intestinal permeability models are summarized, with focus on Ussing chamber and parallel artificial membrane permeability assay. In addition, future trends of permeability models are briefly discussed. This review may provide a reference to accessing permeability of lead compounds.
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To study the intestinal absorption characteristics of drug's nanocrystalline self-stabilizing Pickering emulsion (NSSPE) in situ in rats. Rat single-pass intestinal perfusion model was established, and high performance liquid chromatography (HPLC) was used to detect the concentration of puerarin in rat intestinal perfusion solution, assay the absorption rate constant (Ka) and the intestinal apparent permeability coefficient (Papp) of NSSPE in duodenum, jejunum, ileum, and colon, which were compared with those of raw material, nanocrystal and normal emulsion, respectively. For NSSPE, the Ka and Papp values were in the following order: duodenum>jejunum>ileum (<0.05)>colon (<0.01). However, there was no obvious difference between jejunum and ileum. As compared with raw material, nanocrystal and normal emulsion, the Ka and Papp values of NSSPE in duodenum were significantly higher than those of other three preparations (<0.05); and the Ka and Papp values of NSSPE in jejunum and colon were significantly higher than those of raw material, nanocrystal and normal emulsion (<0.01); and the Ka and Papp of NSSPE in ileum were also higher than those of raw material and normal emulsion (<0.05), but had no obvious difference with nanocrystal. The results showed that NSSPE could significantly improve the absorption of puerarin in the intestine of rats.
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To compare the intestinal absorption of Wuzhuyu decoction(WZYD) between normal rats and migraine model rats, and investigate the optimized WZYD from aspect of absorption. The rat single pass intestinal perfusion test(SPIP) was adopted for optimized sample and un-optimized sample in normal and migraine model rats induced by nitroglycerin and reserpine. The contents of 8 ingredients were determined by high performance liquid chromatography(HPLC), and 4 absorption parameters for each ingredient were calculated and compared: unit area absorption(Mper area), absorption rate constant(Ka), apparent coefficient(Papp) and relative absorption rate(RA). The results showed that there was a great difference between normal rats and model rats in the intestinal absorption of the same WZYD. As compared with normal rats, the absorption parameters of most ingredients in optimized sample were increased in migraine model rats induced by nitroglycerin; Similar phenomena were also found in migraine model rats induced by reserpine. However, the absorption parameters of most ingredients were decreased in un-optimized sample. Therefore, pathological model rats shall be used for effective ingredient recognition based on the correlation between intestinal absorption spectra and pharmacological effects. As compared with the un-optimized samples, the absorption of effective ingredients was faster, easier and more adequate in the optimized samples, revealing their mechanism on better efficacy from the aspect of absorption.
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OBJECTIVE:To study absorption characteristics of naringin in situ single-pass intestinal perfusion model of rats. METHODS:UPLC method was established for the content determination of naringin and naringenin in intestinal perfusion samples of rats. The in situ single-pass intestinal perfusion model of rats was adopted to investigate intestinal(duodenum,jejunum,ileum and colon)absorption and metabolic characteristics [apparent permeability coefficient(Peff),absorptivity,metabolic rate] of naringin(10 μ mol/L). RESULTS:The linear range of naringin and naringenin were 1.25-40,1.25-40 μ mol/L(R2=0.999 4, 0.996 6). The detection limit were 0.5,0.4 μ mol/L,and limit of quantitation were all 1.25 μ mol/L. Precision of inter-day and intra-day,recovery and stability in HBSS solution,perfusion fluid of small intestine and colon were all in line with the standard. Peffof naringin in duodenum,jejunum,ileum and colon of rats were(0.28 ± 0.19),(0.71 ± 0.17),(0.30 ± 0.02),(0.59 ± 0.19) (n=6),without statistical significance(P>0.05).Absorptivities were(2.90±2.14)%,(6.38±3.61)%,(3.69±0.56)%,(6.64± 2.12)%(n=6). Naringin could be metabolized to naringenin in 4 intestinal segments of rats,with metabolic rate of(2.98 ± 1.51)%,(2.53 ± 1.31)%,(2.24 ± 1.33)%,(0.70 ± 0.20)%(n=6). The lowest absorptivity and the highest metabolic rate of naringin were occurred in the duodenum,there were statistical significance compared with colon(P<0.05). CONCLUSIONS:Naringin shows poor permeability and poor absorption in the intestinal tract of rats.There was no specific absorption site in the rat' s intestines for naringenin;naringin could be metabolized to naringenin in small intestine and colon,but metabolic rate of naringin in small intestine is higher than in colon.
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Aim To study the characteristics of in vitro release and in situ absorption of evodiamine load-ed microemulsion (EDM).Methods EDM was pre-pared, its release in pH 1.2 HCl solution and pH 6.8 phosphate buffer solution were studied by dialysis , and the cumulative release rates were calculated .The sin-gle-pass intestinal perfusion was used to study the ab-sorption of EDM in duodenum , jejunum , ileum and co-lon, the absorption in stomach was also studied , and the absorption rate constant ( Ka ) and effective perme-ability (Pef ) of the drug were calculated.The concen-tration of ED was measured by HPLC .Results The cumulative release rate of EDM and ED in pH 1.2 HCl solution was ( 64.76 ±0.73 )％, ( 13.98 ±0.49 )％, respectively , and that of EDM was 4.63 times of ED . In pH 6.8 phosphate buffer solution the cumulative re-lease rate was ( 91.72 ± 0.51 )％, ( 18.34 ± 0.20)％, respectively, which was 5.01 times of ED. The Ka of EDM was more than 3 times of ED, and Pef was more than 2 times of ED .Conclusion Microe-mulsion can improve in vitro release and in situ absorp-tion of ED.
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To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻⁴ cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻⁴ cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.
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Aim To prepare the novel pyridostigmine bromide nanoemusion(PPNE)and study its release in vitro, and to investigate the intestinal absorption. Methods Pyridostigmine bromide (PB)and PPNE were tested by HPLC in pH 1 .2 HCl,pH 6.8,pH 7.4,pH 7.8 PBS.Rat single pass intestinal perfusion method was employed to investigate the absorption mechanism of PB and PPNE.Results PB release rate was faster than PB in the four release media;the intes-tinal absorption rate constant(Ka )and apparent perme-ability coefficient(Papp)of PPNE were increased in the duodenum,jejunum,ileum and colon segments.PB and PPNE had significant difference in the duodenum, jejunum,ileum and colon segments by t test (P <0.05).Conclusions PPNE can improve the bioavail-ability of drugs,increase the drugs permeability,sig-nificantly improve the absorption of the drugs in the in-testinal segments. PPNE has obviously sustained effects.
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Objective To investigate the pharmacokinetic behavior and in situ intestinal absorption of evodiamine complex water-in-oil nanoemulation (WECNE). Methods WECNE was formulated with the titration stirring methods. Twelve male SD rats were intragastrically administered with evodiamine (EDA) and WECNE at the same EDA dose of 100 mg • kg-1. Blood samples were collected from eye socket at 0. 083, 0. 25, 0. 5, 0. 75, 1, 2, 5, 8, 12, 24, 48 and 72 h after intragastrical administration, and the plasma concentrations of EDA were determined by RP-HPLC. DAS 2. 1. 1 software was applied to evaluate the pharmacokinetic behavior. Single-pass intestinal perfusion was carried out to test the intestinal absorption in situ. Results The area under the curve (AUC0-72h), peak concentration (Cmax) and time to peak (Tmax) of WECNE were (4 924. 59 ± 1 105. 28) μg • L • h-1, (305. 47 ±51. 23) μg • L-1 and (0. 83 ± 0. 29) h, respectively. The absorption rate constant (Ka) of WECNE in the stomach, duodenum, jejunum, ileum and colon were (1. 05±0. 82)×10-5, (12. 19± 1. 57) × 10-5, (12. 66± 1. 35) × 10-5, (11. 94±4. 17) ×10-5 and (11. 21 ± 1. 25) × 10-5 L • s-1, respectively. In addition, the effective permeability (Peff) of WECNE in the duodenum, jejunum, ileum and colon were (26. 03 ± 3. 84) × 10-5, (18. 48±5. 99) × 10-5, (19. 77 ± 2. 59) × 10-5 and (36. 02±1. 48) × 10-5 cm • s-1, respectively. Conclusion WECNE can improve the bioavailability and the absorption in situ of EDA in different parts of the gastrointestinal tract.
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Objective: To compare intestinal absorption features of berberine hydrochloride phospholipid solid dispersions (BBH-PSD) by rat single-pass perfusion model, and to explore the mechanism of berberine bioavailability increasing mechanism by phospholipid solid dispersion technology. Methods: The single-pass perfusion model was established in rats, the concentration of berberine in intestinal perfusion was determined by HPLC, and phospholipid solid dispersion technology promoting intestinal absorption of berberine was investigated. Results: Compared with berberine, BBH-PSD could promote much more absorption of berberine in various intestinal segments, especially in jejunum, and the mechanism was related to improving permeability and strengthen simple diffusion of berberine. The Ka and Papp values of BBH and BBH-PSD in jejunum were obviously higher than BBH (P < 0.05); When the volumetic flow rate of BBH-PSD was 0.2, 0.4, and 0.8 mL/min, Ka and Papp were both higher than BBH (P < 0.05); The increasing mass concentration was not obvious to intestinal absorption of BBH, while the increasing mass concentration of BBH-PSD obviously increased the intestinal absorption of BBH (P < 0.05). Conclusion: Intestinal absorption characteristics of berberine phospholipid solid dispersion is beneficial to improve berberine oral bioavailability, and it can provide a scientific basis for the development of new dosage forms of berberine hydrochloride.
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Objective: To explore the intestinal absorption characteristics of tanshinone components self emulsifying drug delivery system (SEDDS). Methods: In situ single-pass perfusion method was used to investigate the absorption characteristics of cryptonshinone, tanshinone I, and tanshinone IIA in rats. The absorption parameters (Ka, Papp) of cryptotanshinone, tanshinone I, and tanshinone IIA were used as indicators to study their optimum absorption site among duodenum, jejunum, ileum, and colon. The effects of verapamil hydrochloride (P-glycoprotein inhibitor, P-gp inhibitor), probenecid (multi-drug resistant protein MRP2), and 2, 4-dinitrophenol (energy inhibitor) on the absorption of cryptonshinone, tanshinone I, and tanshinone IIA were also studied, as well as the effects of their different concentration. Results: Cryptonshinone, tanshinone I, and tanshinone IIA could be absorbed at all four intestinal segments, and the optimum absorption site was the upper segment of small intestine. The absorption of cryptotanshinone and tanshinone I were concentration-dependent at experimental concentration levels (1.05-4.19 mg/L and 1.22-5.56 mg/L), while tanshinone IIA was not affected obviously by its concentrations (2.43-11.12 mg/L). Verapamil hydrochloride had no significant influence on the absorption of cryptotanshinone or tanshinone I, while the absorption of tanshinone IIA was improved remarkably. Probenecid increased the absorption of cryptonshinone and tanshinone I apparently, while had no obvious effect on that of tanshinone IIA. 2,4-Dinitrophenol could decrease the absorption of cryptonshinone, tanshinone I, and tanshinone IIA apparently. Conclusion: Cryptonshinone and tanshinone I are supposed to be the substrate of MRP2 instead of P-gp. Tanshinone IIA is supposed to be the substrate of P-gp, instead of MRP2. The energy participated in the absorption of cryptonshinone, tanshinone I, and tanshinone IIA. Active absorption maybe also involved in the absorption of cryptonshinone, tanshinone I, and tanshinone IIA.
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Objective: To investigate the characteristics of intestinal absorption of glycyrrhetinic acid in rats in the multicomponent environment. Methods: The effect of multicomponent environment on intestinal absorption of glycyrrhetinic acid was investigated in rat model of in situ single-pass intestinal perfusion, HPLC was used to determine the concentration of glycyrrhetinic acid in intestinal perfusion fluid samples, the effective permeability coefficient (Peff), absorption rate constant (Ka), and absorption fraction (Fa) of glycyrrhetinic acid in rats ileum were calculated, the effects of glycyrrhetinic acid with different mass concentration and P-glycoprotein (P-gp) inhibitor verapamil, as well as the compatibility of different components on intestinal absorption of glycyrrhetinic acid were examined,. Results: The Peff, Ka, and Fa values of glycyrrhetinic acid perfusion liquid (10 and 20 µg/mL) in the ileum segment had no significant difference. Added with 100 µmol/L verapamil, Peff, and Fa values of 10 µg/mL glycyrrhetinic acid increased, which illustrated that the glycyrrhetinic acid might be the substrate of P-gp; In two components compatibility, the effect of baicalin on absorption of glycyrrhetinic acid was the most obvious, Peff value of glycyrrhetinic acid was from (4.05 ± 0.78) × 10-5 cm/s to (2.18 ± 0.63) × 10-5 cm/s, and the penetration of glycyrrhetinic acid was reduced. The puerarin consociation baicalin and berberine had no obvious effect on permeability of glycyrrhetinic acid. In the three components compatibility condition, the experimental results showed that after glycyrrhetinic acid combined with puerarin and berberine, the permeability coefficient did not change, while the permeability coefficient changed, but not obviously, glycyrrhetinic acid combined with baicalin and berberine had lower permeability, Peff values were from (4.05 ± 0.78) × 10-5 cm/s down to (1.35 ± 0.69) × 10-5 cm/s, and the effects of baicalin on glycyrrhetinic acid was evident. Conclusion: Glycyrrhetinic acid can be absorbed in the ileum of rats, and has no obvious influence on Peff and Ka values within a certain range of quality concentration. The absorption mechanism is determined to be passive diffusion, glycyrrhetinic acid is substrate of P-gp, and saturation phenomenon exists transporters; Baicalin has significant effects on glycyrrhetinic acid absorption, which may be related to the induction by P-pg expression, increasing the glycyrrhetinic acid from cell to the extracellular discharge, reducing the penetration of glycyrrhetinic acid, and influencing the absorption.
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Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (<0.01). The absorption rate constant () and the apparent permeability coefficient () for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values ofandof Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration () of the blocking model were significantly lower than those of the control model (<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.