Homma M, Oka K, Ikeshima K, Takahashi N, Niitsuma T, Fukuda T, Itoh H
Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
J Pharm Pharmacol. 1995 Aug;47(8):687-92. doi: 10.1111/j.2042-7158.1995.tb05861.x.
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.
三种主要的中药，小柴胡汤、柴朴汤和赛雷托，由含有甘草酸的相似草药配方组成，甘草酸是11β-羟基类固醇脱氢酶的强效抑制剂。我们在健康受试者中进行了交叉开放试验，以阐明这些制剂联合使用时泼尼松龙的药代动力学。所有受试者在口服其中一种试验制剂前，单次口服10mg泼尼松龙。经过2周的洗脱期后，他们以7.5或9.0g的日剂量接受其中一种试验制剂治疗三天。在研究的第三天，将10mg泼尼松龙与试验制剂联合口服。小柴胡汤组治疗前后泼尼松龙的曲线下面积（AUC）从0.94mg·h·L-1降至0.78mg·h·L-1（P<0.05），柴朴汤组从0.92mg·h·L-1增至1.06mg·h·L-1（P<0.01），赛雷托组未发生变化。反映11β-羟基类固醇脱氢酶活性的泼尼松和泼尼松龙的AUC比值，在小柴胡汤组治疗后升高（P<0.01），在柴朴汤组降低（P<0.01），赛雷托组未发生变化。内源性可的松与皮质醇的比值也观察到类似结果。由于三种制剂中甘草酸含量相同，三组之间11β-羟基类固醇脱氢酶效应不同出乎意料。这些观察结果表明，一些未知的代谢酶调节剂、促进剂或抑制剂可能参与了这些传统治疗。
