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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.
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Animals , Rats , Drugs, Chinese Herbal , Pharmacokinetics , Intestinal Absorption , Intestines , Phytochemicals , PharmacokineticsABSTRACT
Objective The relationship between the in vivo absorption kinetics and the in vitro release kinetics of various components (including flavonoids and terpenoids) contained in Ginkgo biloba extract (GBE) sustained-release pellets were evaluated using multi-component integration kinetics which could provide a reference for more accurate assessment of in vitro and in vivo correlation. Methods The release rates in vitro of main ingredients (quercetin, isorhamnetin, bilobalide, ginkgolide A, ginkgolide B and ginkgolide C) were detected by HPLC-MS/MS. The integrated drug concentration was calculated, and the release rates in vitro of integrated components were then depicted according to the results. Plasma was collected at different time points after oral administration of GBE sustained-release pellets, multiple components contained in GBE sustained-release pellets were then determined. A novel approach of self-defined weighting coefficient (Wj) based on the area under the curve from zero to infinity AUC0—∞ had been created to obtain the holistic pharmacokinetic profiles of GBE sustained-release pellets. To evaluation the in vitro-in vivo correlation of GBE sustained-release pellets, the percent of integrated in vivo absorption calculated by the Wagner-Nelson methodwas plotted versus the percent of integrated in vitro drug release at the same time. Results The components contained in sustained- release pellets had a good release, the Wj of each component in GBE sustained-release pellets were as follows: quercetin, 0.248 1; isorhamnetin, 0.009 2; bilobalide, 0.228 2; ginkgolide A, 0.296 4; ginkgolide B, 0.132 4; ginkgolide C, 0.090 3. The in vivo-in vitro correlation equation was Y = 0.930 8 X + 12.84, r = 0.962 9, indicated that the correlation between in vivo absorption kinetics and in vitro release kinetics is good. Conclusion The efficacy of the herbal medicines depends on a variety of components combined effect, using the integrated pharmacokinetic to analyze IVIVC could take the characteristic of each component into account, which is helpful for the study of the correlation between in vivo absorption kinetics and in vitro release kinetics.
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Objective To explore absorption kinetics of roxatidine acetate hydrochloric (ROX) in intestine of rats.Methods The absorption kinetics and permeability of ROX under different concentrations and different intestinal segments were investigated by double wavelength spectrophotometry via the in situ perfusing method in rats.Results There was no significant difference in Ka of ROX under different concentrations.The absorption rate in rats descended in order of duodenum,jejunum,ileum and colon [(3.87±0.12)×10-2,(2.53±0.18)×10-2,(1.43-±0.10)×10-2,(0.91±0.15)×10-2 · h-1].Conclusion The absorption of ROX in intestine complies with the passive transport mechanism and first order kinetics.ROX is well absorbed in thewhole intestine.
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OBJECTIVE: To investigate the absorption kinetics of Panax notoginseng saponins (PNS) in rat small intestines and the effects of bioadhesive materials on the absorptive kinetics and appearance permeability. METHODS: HPLC was used to determine the concentrations of Panax notoginseng saponins. An in situ single pass intestinal perfusion was used to investigate the absorption of Panax notoginseng saponins in rat small intestines (duodenum and jejunum-ileum). RESULTS: In duodenum and jejunum-ileum, Panax notoginseng saponins at different concentrations (0.5-2 mg · mL-1) had no significant effect on the absorptive kinetics and appearance permeability of small intestines (P > 0.05), respectively. Some bioadhesive materials (include chitosan, carbomer 934P, 941P, Konjac glucan and HPMC K4M) could promote the absorption of Panax notoginseng saponins in small intestines, this effect was more obvious in duodenum area. HPMC K15M has no effect on the PNS absorption in small intestines(P > 0.05), pectin could even delay the absorption to some extent. CONCLUSION: Panax notoginseng saponins has a poor absorption in small intestines, the passive diffusion mechanism take great part in its transport progress. Some bioadhesive materials could enhance the permeability of Panax notoginseng saponins on the small intestine wall.
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Objective To explore the absorption properties and kinetics of nicorandil from small intestinal segments. Methods The absorption kinetics and permeability of nicorandil under different conditions were investigated by HPLC via the in situ perfusing method in rats. Results There was no significant difference in Ka of nicorandil under different concentrations and different pH.The absorption rate in rats descended in order of jejunum,duodenum,ileum and colon, as (4.69±0.05)×10-2 ,(3.35 ±0.04) × 10-2 ,(2.66± 0.05) × 10-2 and (0.89± 0.08) × 10-2 .h-1 . Conclusion The absorption of nicorandil in intestine complies with the passive transport mechanism and first order kinetics.Nicorandil is well absorbed in the whole intestine and can be prepared as delayed release and controlled release forms.
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This review analyzed domestic and foreign literatures on intestinal absorption,introduced the current methods and models commonly used in phenolic glycosides researches and their impacts focused on intestinal absorption,summarized the research status,aims to provide a reference for improving their oral bioavailability,improve formulations,new medicine and clinical rational use of phenolic glycosides.
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OBJECTIVE: To explore the stomach and intestine absorption kinetics of chlorogenic acid in rats. METHODS: In situ perfusion model was employed to investigate the absorption characteristics of chlorogenic acid in rats. Ultraviolet spectrophotometry and HPLC method were used for phenolsulfonphthalein and chlorogenic acid determination respectively. RESULTS: The absorption rate per hour of chlorogenic acid(40 μg · mL-1) in stomach was 7.77%. The intestinal absorption rate constants of chlorogenic acid at concentration of 20, 40 and 80 μg · mL-1 were 0.0521, 0.052 5 and 0.0472 h-1 respectively. The intestinal absorption rate constants at duodenum, jejunum, ileum, and colon were 0.0492, 0.0395, 0.0630 and 0.0318 h-1, respectively. After the bile duct was ligated, the intestinal absorption rate constant of chlorogenic acid at 40 μg · mL-1 was 0.0662 h-1. CONCLUSION: Drug concentration has no dramatic influence on the intestinal absorption of chlorogenic acid in rats. The absorption mechanism is passive absorption and complies with first-order kinetics process. The absorption at duodenum and ileum is better than that at jejunum and colon. Bile excretion has no effect on absorption of chlorogenic acid in rats.
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OBJECTIVE: To investigate the absorption kinetics of fenofibrate nanosuspension in rat intestine. METHODS: The intestine of rats was cannulated for in situ recirculation. UV spectrophotometry was used to determine the concentrations of phenol red while HPLC was used to determine the concentrations of fenofibrate and fenofibric acid. RESULTS: The fenofibrate nanosuspension exhibited substantial absorption enhancement in entire intestine compared to the crude drug solution. The difference in drug absorption at concentrations from 50 to 200 μg · mL-1 between fenofibrate nanosuspension and crude drug solution was not significant. Different pH values of K-R buffer had no effect on the intestinal permeability (Papp) and absorption rate constant (KR) for the two dosage forms. The absorption rate constants (h-1) of fenofibrate nanosuspension at duodenum, jejunum, ileum and colon were (0.373 ± 0.0021), (0.329 ± 0.0008), (0.362 ± 0.0014), and (0.347 ± 0.0079), respectively. CONCLUSION: Fenofibrate nanosuspension can be well absorbed in the whole intestinal segments. The absorption of fenofibrate nanosuspension in rat intestine is a first order process with passive diffusion mechanism.
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Objective: To investigate the rat intestinal absorption kinetics of danshensu (DS) and protocatechuic aldehyde (PA) in Salviae Miltiorrhizae Radix et Rhizoma extract. Methods: In situ single pass intestinal perfusion model was employed to investigate the effects of perfusion rate, perfusion solution pH value, bile duct ligation, drug concentrations, absorption sites and P-glycoprotein (P-gp) on absorption of DS and PA, and perfusion volume was corrected by gravimetric method. Meanwhile, the concentration of DS and PA in the perfusate were determined by HPLC. Results: The drug absorption constant (Ka) and apparent absorption coefficient (Papp) of DS and PA increased linearly along with the increasing perfusion rates among the ranges of 0.2-0.8 mL/min. pH value of perfusion solution affected drug absorption (P < 0.05), Ka and Papp of DS and PA decreased with increasing pH value at pH values of 7.4, 6.8, and 5.5. And at pH value of 5.5 and 6.8, the absorption had no significant difference, but there was significant difference at pH value between 5.5 and 7.4 (P < 0.05). There was no significant difference in Ka and Papp value between bile duct ligation group and no ligation group. At different absorption sites, K a and Papp of DS in the duodenum, jejunum, ileum, and colon sequence have a downward trend, but not for PA, while PA could be absorbed well at all intestinal segments. In the drug concentrations of 0.8, 1.5, and 2.2 mg/mL, Ka, and Papp of DS decréased with higher concentrations, and PA absorption parameter has non-obvious changes. There was no significant difference in Ka and Papp between the presence of P-gp inhibitor and no P-gp inhibitor. Conclusion: Perfusion rate and pH value have significant influence on absorption of DS and PA. Two water-soluble ingredients could be absorbed at all intestinal segments and DS has better absorption at former intestinal segments. The concentration of the extract has no influence on its absorption parameters of PA, which preliminarily demonstrates that PA is absorbed by passive diffusion mechanism. However, absorption of DS is affected by concentration, indicating that in addition to passive diffusion, it may also have active absorption or facilitation diffusion in absorption process of DS. Moreover, two ingredients are not affected by P-gp efflux.
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To investigate the absorption kinetics characteristics of icariin for various intestinal segments.Methods: To establish the situ intestinal perfusion model and to study the absorption of icariin for various intestinal segments.Results: Icariin was metabolized quickly in the four intestinal segments.The permeability coefficient(P*eff) were(4.27?0.28),(5.25?0.17),(1.99?0.09),(0.80?0.03) at duodenum,jejunum,ileum,colon,respectively.Icariside can be detected in the four intestine segments in rats by HPLC.Conclusion: Icariin is metabolized into icariside,and then icariside can be absorbed.
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0.025 63 h-1).A linear relation between absorption and concentration was noted for simvastatin at a concentration of 1.0～20.0 ?g?mL-1;and within a pH value of 5.0～7.4,the absorption of simvastatin was not affected.CONCLUSION:Simvastatin showed absorption behavior in the whole section of intestine.The absorption of the drug conforms to the passive transport mechanism and first-order kinetics.The results indicate that simvastatin can be formulated and prepared into sustained-release drug delivery system.
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OBJECTIVE:To study the interaction of baicalin with berberine for intestinal absorption in rats. METHODS: The mode was induced by in situ intestinal perfusion to observe the absorptive kinetics characteristic in rats’ intestine before and after mixing. RESULTS: The absorption rate constant (ka) and absorption rate (A) of baicalin alone were (0.068?0.002)h-1 and (5.92?1.39)% while those of baicalin mixed with berberine were (0.060?0.002)h-1 and (4.27?1.23)% , respectively. ka and A of berberine alone were (0.044?0.003)h-1 and (3.47?0.64)% while those of berberine mixed with baicalin were (0.057?0.006) h-1 and (5.18?0.83)%, respectively. There were significant difference in the absorption rate constant of baicalin after mixing(P
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Objective To investigate the kinetics of absorbing timosaponin by AB-8 resin.Methods Static absorption experiment,dynamic absorption experiment and series dynamic absorption experiment were carried out,and then the content of timosaponin was detected by spectrophotometry.Finally,the static absorption curve and the dynamic absorption curve were figured out.Results The result of static absorption experiment showed that the parameters of Lagergren equation are Kad=0.0186,r=0.9986,and the parameters of Dumwals-Wagner are K=0.0081,r=0.9958.In dynamic absorption experiment,the leaking of timosaponin is found and the penetrating point is at 600mL(0.1g/mL).Conclusion The mechanism of AB-8 resin absorbing timosaponin is characterized as liquid membrane diffusion at the early phase and intragranular diffusion at the later phase.Leaking phenomena in dynamic absorption experiment can be solved by three tubes in series.Therefore,this method can be used for the research of Chinese herbal medicine.
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0.05).The absorption of NCTD was a first-order process with passive diffusion mechanism.The absorption law in vivo was the same as in vitro,the correlation coefficient between them was 0.999 4.Conclusion NCTD-CS-NP could improve the absorption of NCTD in rat small intestine.NCTD is well absorbed at the superior and middle segments of intestine.The concentration of NCTD has no distinctive effect on the absorption kinetics.The release of drug in vitro and its uptake is well correlated.