Effects of Seijo‐bofu‐to, a Traditional Japanese Herbal Medicine Containing Furanocoumarin Derivatives, on the Drug‐Metabolizing Enzyme Activities in Healthy Male Volunteers

Abstract

Seijo-bofu-to, a traditional medicine used to treat acne in Asian countries, contains twelve herbal components, including Angelica dahurica root, a source of furanocoumarin derivatives. In this study, we investigated potential herb-drug interactions of seijo-bofu-to in healthy male volunteers. Thirty-two young, healthy, non-smoking males were assessed for the baseline activity of cytochrome P450 (CYP) 1A2, CYP3A, CYP2D6, N-acetyltransferase 2 and xanthine oxidase according to the urinary metabolic indices of 8-hr urine samples collected after the administration of a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan, and the ratio of urinary excretion of 6b-hydroxycortisol to cortisol. Thereafter, the volunteers received 3.75 g of seijo-bofu-to twice daily for 7 days and underwent the same tests on post-dose day 7. The geometric mean ratio of the CYP1A2 activity on day 7 to that observed at baseline was 0.66 (95% CI, 0.55-0.79, p = 0.001). The geometric mean phenotypic indices for CYP3A, CYP2D6, N-acetyltransferase 2 and xanthine oxidase on day 7 did not differ from the baseline values. The findings of the present study suggest that seijo-bofu-to may inhibit the activity of CYP1A2, whereas it is unlikely to participate in herbdrug interactions involving medications predominantly metabolized by CYP3A, CYP2D6, N-acetyltransferase 2 or xanthine oxidase.

The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers

“…The urinary concentrations of three caffeine metabolites [1,7-dimethyluric acid (17U), 1-methyluric acid (1U) and 1-methylxanthine (1X)], DM and three DM metabolites [dextrorphan (DX), 3-methoxymorphinan (MM) and 3-hydroxymorphinan (HM)], 6β-HC and FC were quantified by HPLC according to a previously described method. [23][24][25][26][27] 5-Acetyl-amino-6-formylamino-3-methyluracil (AFMU) was completely converted to 5-acetyl amino-6-amino-3-methyluracil (AAMU) under condition of a pH of 10, and then the AAMU was measured by HPLC according a previously described method. [23][24][25][26][27] Statistical Analysis The levels of CYP1A2, CYP2D6, CYP3A, NAT2 and XO activities were assessed according to the methods of our previous reports, using the following equations.…”

“…[23][24][25][26][27] 5-Acetyl-amino-6-formylamino-3-methyluracil (AFMU) was completely converted to 5-acetyl amino-6-amino-3-methyluracil (AAMU) under condition of a pH of 10, and then the AAMU was measured by HPLC according a previously described method. [23][24][25][26][27] Statistical Analysis The levels of CYP1A2, CYP2D6, CYP3A, NAT2 and XO activities were assessed according to the methods of our previous reports, using the following equations. [23][24][25][26][27] High index values of CYP1A2, NAT2, XO and CYP3A indicate high activity levels.…”

“…[23][24][25][26][27] Statistical Analysis The levels of CYP1A2, CYP2D6, CYP3A, NAT2 and XO activities were assessed according to the methods of our previous reports, using the following equations. [23][24][25][26][27] High index values of CYP1A2, NAT2, XO and CYP3A indicate high activity levels. Conversely, a high index value of DM/DX indicates a low CYP2D6 activity level.…”

“…Multiple comparisons were corrected using Bonferroni's method, and p values of <0.05/n after correcting for the number of comparisons were considered to indicate statistical significance. Based on the standard deviations of our previous studies, [23][24][25][26][27] it was estimated that the number of volunteers was sufficient for detecting a 50% difference in the log-transformed metabolic indices of the activity of CYP1A2, CYP2D6 and CYP3A between the baseline and day 7 values, with a power of 0.80 (a-level of 0.05). The statistical analyses were performed using the SPSS software program (Version 17.0, IBM Japan Inc., Tokyo, Japan).…”

“…[23][24][25][26][27] In this study, we attempted to evaluate the effects of YKS on the activity of drug-metabolizing enzymes (CYP1A2, CYP3A, CYP2D6, NAT2, XO) in Japanese healthy volunteers using a similar procedure. [23][24][25][26][27] In addition, we investigated the potential effects of YKS on the activities of CYP2D6, CYP1A2 and NAT2 with these common polymorphisms. 28,29) The primary objective of this clinical study was to verify the potential pharmacokinetic interaction of YKS, which is likely to be used in combination with various medicines that are mainly metabolized by the drug-metabolizing enzymes, such as antidementia, antipsychotic and antidepressants.…”