Interaction of Rhei Rhizoma extract with cytochrome P450 3A and efflux transporters in rats.

Traditional Chinese herbal medicines are frequently prescribed in pharmacotherapy in Japan. In the present study, we evaluated the possible interaction of several herbal extracts including Rhei Rhizoma extract with cytochrome P450 (CYP) 3A and efflux transporters such as P-glycoprotein and multidrug resistance-associated protein (MRP) 2. Rhei Rhizoma extract (100 microg/ml) significantly suppressed the CYP3A-mediated 6beta-hydroxylation of testosterone in hepatic microsomes, and increased the extent of bioavailability of midazolam, a typical CYP3A substrate, in rats. Also, Rhei Rhizoma extract (300 microg/ml) significantly suppressed P-glycoprotein-mediated efflux transport of rhodamine 123 (Rho123) in rat everted intestine. In an in-vivo study, Rhei Rhizoma extract added to intestinal perfusate at a concentration of 300 microg/ml significantly suppressed the intestinal exsorption of Rho123, though it exerted no effect on the biliary excretion of Rho123. Furthermore, the in-vitro and in-vivo MRP2-mediated intestinal efflux of 2,4-dinitrophenyl-S-glutathione was significantly suppressed by Rhei Rhizoma extract (1000 microg/ml). In conclusion, Rhei Rhizoma extract, which is taken orally at doses of 0.5-1 g each or 1-3 g daily in clinical practice, may cause pharmacokinetic herb-drug interactions in the process of the intestinal and/or hepatic CYP3A-mediated drug metabolism and P-glycoprotein- and/or MRP2-mediated efflux transport in the intestine.

[Mechanism of protective effects of ouren-gedoku-to and san'ou-syashin-to on the gastric mucosa].

Ouren-Gedoku-To (OGT) and San'ou-Syashin-To (SST), traditional Chinese prescriptions, have been used to treat peptic ulcer. In order to elucidate the mechanism of the protective effects of OGT and SST on the gastric mucosa, we studied their effects on gastric mucosal lesions, ion permeability and prostaglandin synthesis using ulcer experimentally induced in rats by saturation with acidic test solution after taurocholate treatment. Both OGT and SST inhibited taurocholate-induced gastric mucosal lesions in a dose-related manner. These prescriptions dose-dependently inhibited not only the increase of hydrogen and sodium ion net fluxes but also possible hydrogen ion back diffusion into the gastric mucosa during saturation with acidic test solution. SST induced a significant increase in gastric mucosal prostaglandins synthesized from 14C labeled arachidonate. These results suggest that both OGT and SST by strengthening the gastric mucosal barrier demonstrate their protective effects on the gastric mucosa and that this effect of SST is attributable to the increased ability of the gastric mucosa to synthesize prostaglandin.

[Prognosis of intra-arterial chemo-embolization in metastatic liver cancer].

We treated 63 patients (pts) suffering from metastatic liver cancer with intra-arterial infusion chemotherapy, and analysed 44 of their for survival since the first treatment with regard to the primary foci of cancer and the method of intra-arterial therapy. Via the superficial femoral artery, we performed superselective hepatic catheterization by Seldinger's method. Three types of intraarterial therapy were used: Gelfoam embolization with mitomycin-C (MMC) in 12 pts (GS-TAE), capillary chemo-embolization with MMC-Lipiodol emulsion in 28 pts (LP-TAI) and "one-shot" slow infusion of MMC or cisplatinum in 4 pts. Fifty-percent survival was 189 days in pts with metastases from colo-rectal cancer (n = 20), 109 days from gastric cancer (n = 9), 100 days from pancreatobiliary cancer (n = 5) and 240 days from breast cancer (n = 7). More than one-year survival was obtained in 13 out of the 40 pts (32.5%). Survival of 12 pts, treated with GS-TAE regimen, was not significantly superior to that of 28 pts with LP-TAI regimen. Hence, we conclude that LP-TAI is the treatment of choice in chemo-embolization for unresectable liver metastases, because it causes less damage to the hepatic arterial beds, and facilitates repeat intraarterial therapy in these pts.

[Preoperative chemoembolization of iopamiron-solved adriamycin and lipiodol on hepatocellular carcinoma--clinicopathological study of ten surgical cases].

Preoperative chemoembolization was performed in 10 patients with hepatocellular carcinoma. The therapeutic regimen included Adriamycin (ADM) solved in nonionic contrast media, Iopamiron and Lipiodol (LP). Two to four ml of the solution, containing 20-40 mg of ADM, was mixed with 5-10 ml of LP by "pumping" method. This emulsion was infused superselectively into the hepatic artery by the balloon-occluded method. The regimen contained no permanent embolic material (e.g., Gelfoam or Ivaron). Dense deposition of LP in the tumor was seen on the CT scan 3-4 weeks after TAI. Surgical specimens, resected 3-12 weeks after TAI, revealed total necrosis of the tumor in 4 cases, subtotal necrosis (more than 80% on the cut surface) in 3 cases, and partial necrosis (less than 80%) in 3 cases. Tumor invasion in the fibrous capsules was necrosed in 4/7 of the cases. Tumor thrombi in the portal vein were also necrosed in 2/4. Our new method is more effective than the previous ones of LP and ADM without Iopamiron, and is equally effective as the regimen using LP, anticancer drugs, and permanent embolic materials.