ABSTRACT
Objective: To compare the pharmacokinetics in rats and tissue distribution in mice of tanshinone IIA (TNS) lipid microsphere and sodium tanshinone IIA silate (STS) injection after iv injection. Methods: A sensitive and specific RP-HPLC method was established to determine the concentration of TSN and STS in rat plasma and mice tissue. The TSN and STS levels in plasma of rats and tissues of mice were compared after iv single dose administration of TSN lipid microsphere (5.40 mg/kg) and STS injection (7.27 mg/kg), and the results were fitted by pharmacokinetic and statistic analyses. Results: The bioavailability (AUC0-∞) and peak concentration (Cmax) values of TSN were 2.14 and 2.22 folds as those of STS, the clearance (CL), apparent volume of distribution (V), and mean repair time (MRT) values of TSN were lower (P < 0.01), and other pharmacokinetic parameters had no significant deviation. The results on the tissue distribution of TSN and STS in mice showed that the contents of TSN in heart, liver, spleen, lung, and kidney tissues were 1.94, 0.11, 0.98, 1.65, and 0.28 folds as those of STS with the same molar dose, and the content of TSN in brain tissue increased more significantly than that of STS which has not been detected. Conclusion: The pharmacokinetics and tissue distribution of TSN and STS at the same molar dose have significant differences, the AUC and Cmax values of TSN are higher, and the concentration of TSN could be increased in heart, brain, and lung tissues significantly, compared with those of STS.
ABSTRACT
<p><b>OBJECTIVE</b>To study the transport mechanism of baicalin of Scutellariae Radix extracts and the effect of Angelica dahurica extracts on the intestinal absorption of baicalin by using Caco-2 cell monolayer model, in order to analyze the effect mechanism of Angelica dahurica extracts on the intestinal absorption of baicalin.</p><p><b>METHOD</b>The Caco-2 cell monolayer model was established with human colonic adenocarcinoma cells, and used to study the effect of pH, time, drug concentration and temperature on the transport of baicalin in Scutellariae Radix extracts, the effect of P-gp and MRP protein-dedicated inhibitors on the bidirectional transport of baicalin in Caco-2 cell model, and the effect of angelica root extracts on baicalin absorption and transport.</p><p><b>RESULT</b>Baicalin was absorbed well at 37 degrees C and under pH 7.4 condition and concentration dependent. Its proteins became inactive at 4 degrees C, with a low transport. The bi-drectional transfer PDR was 0. 54. After P-gp inhibitor verapamil and MRP inhibitor probenecid were added, the value of PappBL-AP of baicalin decreased, but without any difference in PDR. The transport of baicalin was improved by 2.34, 3.31 and 3.13 times, after A. dahurica extract coumarin, volatile oil, and mixture of coumarin and volatile oil.</p><p><b>CONCLUSION</b>The transport mechanism of baicalin is mainly passive transfer and supplemented with efflux proteins involved. A. dahurica extracts can enhance the absorption of baicalin, which may be related to the passive transfer merchanism of baicalin. A. dahurica extracts' effect in opening the close junction among cells may be related to its expression or function in inhibiting efflux proteins.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Angelica , Chemistry , Biological Transport , Caco-2 Cells , Cell Line, Tumor , Coumarins , Chemistry , Pharmacology , Drug Interactions , Drugs, Chinese Herbal , Chemistry , Pharmacology , Flavonoids , Pharmacokinetics , Intestinal Absorption , Physiology , Oils, Volatile , Chemistry , Pharmacology , Plant Extracts , Chemistry , Pharmacology , Plant Roots , Chemistry , Probenecid , Pharmacology , Scutellaria baicalensis , Chemistry , Verapamil , PharmacologyABSTRACT
To explore the mechanism of the absorption enhancement of Angelica dahurica extract (Ade), the absorption mechanism of baicalin in the Scutcllaria water extraction as well as the effect of Angelica dahurica extract on absorption of baicalin were investigated. In order to determine the main absorption site, everted intestinal sac model was used to study the effect of Angelica dahurica extract on the absorption of baicalin at duodenum, jejunum, ileum and colon. In situ single pass intestinal perfusion model was performed to study the absorption of various concentrations of baicalin and the effect of Angelica dahurica extract on the absorption of baicalin at the main absorption site. To authenticate the consequence of perfusion by getting the blood from the hepatic portal vein and determine the concentration of the baicalin in the blood. The result showed that baicalin could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: ileum > colon > jejunum > duodenum. The absorption ofbaicalin in the duodenum significantly increased with Angelica dahurica extract, thus, duodenum was chosen to be the studying site. Apparent permeability values (Papp) and absorption rate constant (Ka) of baicalin in the duodenum increased gradually with higher concentrations. When the concentration of baicalin rises to a certain degree, the absorption increase had a saturable process, the absorption of baicalin may be an active transportation. Baicalin may be not a substrate of P-gp as verapamil which had not significantly affected the Papp and Ka of baicalin. The absorption of baicalin in the duodenum significantly increased (P < 0.01) in the two models with Angelica dahurica extract and the concentration of baicalin in the blood from the hepatic portal vein showed that the Angelica dahurica extract can increase the absorption of baicalin.