Repetitive administration of Shaoyao-Gancao-tang to rats restores the bioavailability of glycyrrhizin reduced by antibiotic treatment

Abstract

Shaoyao-Gancao-tang (SGT), a traditional Chinese formulation, is often used together with antibiotics such as amoxicillin and metronidazole (AMPC-MET) for the treatment of peptic ulcers in Japan. However, the bioavailability of glycyrrhizin (GL) in SGT is severely reduced by a single administration of AMPC-MET, and the reducing effect continues for 12 days. GL is one of the major pharmacologically important glycosides in SGT and is transformed into the active metabolite 18beta-glycyrrhetic acid (GA) by intestinal bacteria in the gut, followed by absorption of the latter into the blood. In order to reduce the negative effect of AMPC-MET on the bioavailability of GL, the optimum scheduling of the medications was examined. We found that the reduction in the plasma GA concentration and the GL-metabolizing activity in faeces caused by a single dose of AMPC-MET could be sharply attenuated by the repetitive administration of SGT for 4 days. The GA concentration and the GL-metabolizing activity were strongly enhanced by further continuous administration of SGT. These findings suggest that repetitive administration of SGT starting 1 or 2 days after the administration of AMPC-MET speeds the recovery of the bioavailability of GL in SGT. Similar strategies for administering medications may also be useful for combination therapy of antibiotics with other traditional Chinese formulations containing bioactive glycosides.

Glycycoumarin from Glycyrrhizae Radix acts as a potent antispasmodic through inhibition of phosphodiesterase 3

“…Voucher sample was deposited in the Department of Kampo-Pharmaceutics, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University. The Glycyrrhizae Radix (6 g of the dried, crushed root) was extracted by boiling in water (600 ml) until the water volume has been reduced by half (He et al, 2003). The extract (5 g from threetimes extract in 30 ml water), which showed an IC 50 value of 358 g/ml for the tonic contraction of mouse jejunum with CCh, was applied to Sephadex LH-20 (Amersham Biosciences, Piscataway, NJ), eluted initially with water, and then with gradually increasing proportions of ethanol (5%, 10%, 20%, 40%, 60%, 80% and 100%), as reported previously (Majima et al, 2004).…”

Preparation of Knockout Extract for Determination of Really Active Compound Using MAb

“…Fig. (6) shows the chemical structure of GC; it is a triterpenoid saponin that can be converted into glycyrrhetic acid (GA) by GC--glucuronidase [28].…”

Bioavailability of glycyrrhizin from Shaoyao-Gancao-Tang in laxative-treated rats

“…In the group without SGT, SGT extract was administered at a single dose at 1400 h on day 0. Blood samples were collected 9 h after SGT administration at 1400 h on day 0 and at 0900 h from days 1 to 9 as reported previously (He et al 2003 initial time point), 1400 and 1900 h on day 0 and at 0900 h from days 1 to 9. The water content in faeces was determined by calculating the weight reduction of faecal samples before and after drying at 120 C for 4 h. The condition was defined as diarrhoea when the water percentage in the faeces was 80% or more.…”

“…However, to date, no study has reported the interactions between SGT and the co-administered sodium picosulfate. As a part of our ongoing biopharmaceutical analysis of the interactions between traditional Chinese formulations and synthetic drugs (He et al 2003), this study was designed to examine the interactions between SGT and sodium picosulfate, by focusing on the intestinal metabolism of glycyrrhizin and the resulting influences on the bioavailability of GA from SGT.…”