ABSTRACT
@#In order to reveal the intestinal absorption mechanism of saikosaponin d (SSd) in vitro and in vivo, the current research investigated the effects of different experimental conditions (time, concentration, temperature, pH, intestinal segments), transporter inhibitors, paracellular pathway enhancer, metabolic enzyme inhibitors on the intestinal absorption of SSd, in Caco-2 monolayers and a single pass perfusion model in rats.The results showed that the apparent permeability coefficient (Papp) and effective permeability coefficient (Peff) of SSd were 4.75 × 10-7 - 6.38 × 10-7 cm/s and 0.19 × 10-4- 0.27 × 10-4 cm/s, respectively, indicating that it was a low permeability compound, and that the transmembrane transport of SSd was concentration-dependent (0.5-5 μmol/L) and time-dependent (0-180 min).Ileum was the main absorption site for SSd. Experimental results based on Caco-2 monolayers showed that the P-gp inhibitor and paracellular permeability enhancer significantly increased the absorption of SSd (P < 0.05), which was consistent with the results obtained in rats. Inhibitors of OATPs and OCTs showed different results in vitro and in vivo, which may be related to the lower expression of them in jejunum.In summary, the intestinal absorption of SSd occurs through a carrier-mediated and energy-dependent transport, as well as passive diffusion, and P-glycoprotein plays an important role in the active transport of SSd.
ABSTRACT
To determine the absorption properties and study the intestinal absorption kinetics of poncidin in rats. In situ single pass perfusion model was combined with High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS/MS) method to investigate the intestinal absorption characteristics and calculate absorption parameters with aspects of drug absorption, concentration and perfusion medium. The absorption of poncidin under acid condition at pH 6.5 was more stable, where intestinal enzymes showed little influence on metabolism, and the absorption was significantly higher than that in pH alkaline condition at pH 8.0 (<0.05). Drug concentrations had no significant influence on absorption rate constant of the same intestinal segment Ka and apparent permeability coefficient Papp values of poncidin. Different concentrations of poncidin showed no significant differences in the Ka and Papp values among duodenum, jejunum and colon, but the values were significantly lower than ileum absorption parameters, with significant differences (<0.05). There was no significant effect of verapamil on intestinal absorption of poncidin. The results showed that poncidin could be absorbed at all the studied intestinal segments while ileum seemed to be the best absorption segment in the concentration range of 10-1 000 μg·L⁻¹. The absorption was characterized by a linear dynamic process of passive transport, without absorption saturation. Weak acid environment was helpful for the intestinal absorption of poncidin, and ponicidin was not a substrate of P-glycoprotein (P-gp).
ABSTRACT
Objective: To investigate the intestinal absorption characteristics of five kinds of flavonoids from Hedyotis diffusa extract in rats. Methods: The in situ rat single-pass intestinal perfusion model was used. The contents of rutin, isoquercitrin, quercetin, kaempferol, and quercetin in perfusates were determined by HPLC-DAD, and the rat intestinal absorption parameters of flavonoids were calculated. Results: In perfusion model, the effective permeability coefficients (Peff) of all components were low. The absorption rate constant (Ka) and Peff had no significant difference when the concentration of total flavonoids from H. diffusa was 0.5-4.0 g/L. In the 2.0 g/L concentration, Ka of rutin, isoquercitrin, quercetin, kaempferol, and quercetin were 0.0113, 0.0154, 0.0102, 0.0305, and 0.0275 min-1, respectively; The Ka sequences of rutin and isoquercitrin in different intestinal segments were ileum > duodenum > jejunum ≈ colon and jejunum > duodenum > ileum ≈ colon. Conclusion: The absorption of the five flavonoids from H. diffusae is a first-order process with the passive diffusion mechanism. The absorption rates of each flavonoid are significantly different. The absorption rate of flavonoid glycosides is lower than that of aglycones. The flavonoids from H. diffusa could be absorbed in all the intestinal segments. The best parts of intestine to absorb rutin and isoquercitrin are ileum and jejunum.
ABSTRACT
OBJECTIVE: To investigate the absorption characteristics of dauricine in rat intestine. METHODS: In situ single-pass perfusion model was used and the concentrations of dauricine in perfusate were determined by HPLC. The effects of perfusion rates, intestinal segments and drug concentrations on the intestinal absorption of dauricine were studied. RESULTS: The absorption rate and absorption degree of dauricine increased with the perfusion rates(0.1, 0.2 and 0.4 mL · min-1)(P0.05); at high, middle and low concentrations, the drug absorption rate constants(Ka) were (2.36±0.0073) × 10-2, (3.73 ± 0.0052) × 10-2 and(5.62 ± 0.0136) × 10-2 min-1, respectively, the apparent permeation coefficients(P.,) were(2.02±0.0002) × 103, (3.10±0.0007) × 10-3 and (5.31±0.0010) × 10-3 cm · min-1, respectively, the absorption percentages(P%) were 8.66%, 10.17% and 19.06%, respectively, and the accumulate absorption amount and accumulate absorption percentages of different concentrations at different time were very low. CONCLUSION: The absorption degree of dauricine increases with perfusion rates; there is no specific absorption site in the whole rat intestinal tract; the absorption of dauricine is very poor and the active transport is involved in the absorption mechanism of dauricine.