Inhibitory effect of Aristolochia fruit on Cytochrome P450 isozymes in vitro and in vivo

The mature fruits of Aristolochia debilis, known in China by the name, "Madouling" has been popularly prescribed in Asia, particularly in China, to treat a range of conditions including gynaecological problems, arthritis and wound healing. This study was aimed to evaluate the potential effect of Madouling on the cytochrome P450 [CYP] isozymes in vitro in microsomal fractions and in vivo in rats. The influence of Madouling on CYPs activity was first explored by an in vitro method of estimating levels of four respective metabolites in rat liver microsomes. The results were re-examined in vivo in rats by using a cocktail approach involving the probe drugs theophylline, tolbutamide, chlorzoxazone and dapsone. Pharmacokinetics of the four substrates was used to analyze the activities of the targeting isozymes. In vitro study revealed that Madouling decreased the activity of CYP1A2, 3A1 and 2E1. However, no significant influence on CYP2C6 was found. These results coincided with those of in vivo study to a great degree except that in vivo estimation the herb didn't inhibit CYP1A2 significantly. From the data obtained, Madouling is suggested as a c and idate for clinically significant CYP interactions. Drug co-administrated with Madouling may need dose adjustment.

Effect of raw Radix Rehmanniae on the pharmacokinetics of pioglitazone in rats

Raw Radix Rehmanniae [RRR] is a frequently used traditional Chinese medicine in the treatment of diabetes mellitus according to the statistics on all of the anti-diabetic formulas recorded in New National Traditional Chinese Medicine. Pioglitazone and RRR may be co-administrated for presumably enhanced therapeutic effects because of the common indications. Therefore, the aim of the study was to evaluate the effect of RRR on the pharmacokinetics of pioglitazone in healthy rats and type 2 diabetic rats. The pharmacokinetic effect of RRR on pioglitazone was studied in healthy rats and type 2 diabetic rats. A validated UPLC-MS/MS method was used to analyze the concentration of pioglitazone in blood samples. The pharmacokinetic parameters were calculated using non-compartmental analyses by Winnonlin 5.0.1. In healthy group, the pre-treatment of RRR significantly [P<0.05] reduced the C[max] but enhanced the V/F of pioglitazone; whereas in T2DM group, significant increase of C[max] and decrease of V/F and T[1/2] were found after the rats were pre-treated with RRR. However, AUC[0-t] and CL/F remained unchanged in both healthy group and T2DM group. In conclusion, co-administration with RRR could alter the pharmacokinetic profiles of pioglitazone to statistically significant levels.

Absorption mechanism of oxysophocarpine across Caco-2 cell monolayer mode / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the absorption mechanism of oxysophocarpine across Caco-2 cell monolayer model.</p><p><b>METHOD</b>The safety concentration of oxysophocarpine in Caco-2 cell was first selected by using MTT method. Then the Caco-2 cell monolayers drug transport model was assigned to study the bi-direction transport mechanism of oxysophocarpine by evaluating the influent factors such as time, concentration, pH, P-gp inhibitor of verapamil, on its absorption characterization.</p><p><b>RESULT</b>In the Caco-2 cell monolayer model, the transport volume was correlated positively with the time and concentration of oxysophocarpine, and affected by pH value. Verapamil had no influence on its transport since the transport of oxysophocarpine from apical (AP) to basolateral (BL) was similar to the transport from basolateral to apical.</p><p><b>CONCLUSION</b>The intestinal absorption mechanism of oxysophocarpine was deduced as passive transference by Caco-2 cell monolayer model.</p>