Different Effects of Traditional Chinese Medicines Containing Similar Herbal Constituents on Prednisolone Pharmacokinetics

Abstract

Three major traditional Chinese medicines (TCM), Sho-saiko-To, Saiboku-To, and Sairei-To, consist of similar herbal prescriptions containing glycyrrhizin, which is a strong inhibitor of 11 beta-hydroxysteroid dehydrogenase. We performed cross-over open trials in healthy subjects to clarify prednisolone pharmacokinetics on co-administration of these preparations. All subjects received a single oral dose of 10 mg prednisolone before oral treatment with one of the test preparations. After a 2-week wash-out interval, they received one of the test preparations for three days at daily doses of 7.5 or 9.0 g. On the third study day, 10mg prednisolone was administered orally in combination with the test preparation. Area under the curves (AUC) of prednisolone before and after the treatment decreased from 0.94 to 0.78 mg h L-1 (P < 0.05) in the Sho-saiko-To group, increased from 0.92 to 1.06 mg h L-1 (P < 0.01) in the Saiboku-To group, and did not change in the Sairei-To group. AUC ratios of prednisone and prednisolone, which reflect the 11 beta-hydroxysteroid dehydrogenase activity, increased in the Sho-saiko-To group (P < 0.01), decreased in the Saiboku-To group (P < 0.01), and did not change in the Sairei-To group after the treatments. Similar results were observed in ratios of endogenous cortisone to cortisol. Because of the equal glycyrrhizin content in all three preparations, it was unexpected that the 11 beta-hydroxysteroid dehydrogenase effect was different amongst the three groups. These observations suggest that some unknown metabolic enzyme modifiers, promoters or inhibitors, may be involved in these traditional treatments.

Systematic Analysis of Post-Administrative Saiboku-To Urine by Liquid Chromatography to Determine Pharmacokinetics of Traditional Chinese Medicine

“…The action mechanisms and active components of Saiboku-To have not been clarified yet. Several pharmacological properties were demonstrated: inhibition of histamine release from mast cells (Toda et al, 1988), inhibition of glucocorticoid metabolic enzymes (Homma et al, 1994(Homma et al, , 1995, and suppression of type I and IV allergic reactions in animal models (Nishiyori et al, 1983(Nishiyori et al, , 1985. The contribution of a few of the chemical constituents present in Saiboku-To has been speculated.…”

Interactions of Herbs with Cytochrome P450

“…Other herbal mixtures containing glycyrrhizin have also been reported to influence the pharmacokinetics of prednisolone and tolbutamide. For example, Xiao Chai Hu Tang and Sho-saiko-To decreased the plasma AUC of prednisolone in rats (Homma et al, 1995); whereas Saiboku-To increased it and Sairei-Tohad no effect. Xiao Chai Hu Tang also decreased the plasma concentration of tolbutamide in rats (Nishimura et al, 1998).…”

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

“…Glycyrrhizin is known to increase the plasma prednisolone concentration in humans and is one of the ingredients of three major traditional Chinese formulations, namely Sho-saiko-To, Saiboku-to, and Sairei-To, which all affected prednisolone pharmacokinetics in healthy volunteers [121,122]. …”