Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics.
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.
Homma
M
M
Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Oka
K
K
Ikeshima
K
K
Takahashi
N
N
Niitsuma
T
T
Fukuda
T
T
Itoh
H
H
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D019695:Glycyrrhizic Acid; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020835:Medicine, Kampo; D011239:Prednisolone / Q000493:pharmacokinetics*; D012016:Reference Values
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D006634:Histamine H1 Antagonists; C045086:saiboku-to; C080903:sairei-to; C018142:saiko-keishi-to; D019695:Glycyrrhizic Acid; D011239:Prednisolone; D006034:Glycyrrhetinic Acid