银杏叶片对人药物代谢酶CYP2A6、XO和NAT2活性的影响

目的探讨银杏叶片对人肝脏药物代谢酶CYP2A6、XO和NAT2活性的影响,预测银杏叶片与常用药物的相互作用,指导临床合理用药.方法以咖啡因作为药物代谢酶CYP2A6、XO和NAT2的探针药物,以反相高效液相梯度洗脱法测定30名受试者服用银杏叶前后人尿液内咖啡因5种主要代谢物的相对含量,采用代谢物的比率分别评价人肝脏药物代谢酶CYP2A6、XO和NAT2活性的变化.结果受试者服药前CYP2A6、XO和NAT2平均活性为0.227±0.076、0.723±0.060和0.447±0.172;服用银杏叶片28d后CYP2A6、XO和NAT2平均活性为0.227±0.072、0.728±0.074和0.391±0.147;服药前后酶CYP2A6、XO的活性无显著性差异,酶NAT2的活性有显著性差异.结论银杏叶片可能不会影响其他经CYP2A6、XO酶代谢的药物临床疗效,但是可以影响与之合用经NAT2代谢的药物临床疗效.     

泮托拉唑对人肝脏药物代谢酶CYP1A2、NAT2和XO活性影响的研究

目的:探讨泮托拉唑对人肝脏药物代谢酶CYP1A2、NAT2和XO活性的影响,预测泮托拉唑与常用药物的相互作用,指导临床医师合理用药。方法:以咖啡因作为药物代谢酶CYP1A2、NAT2和XO的探针药物,以反相高效液相梯度洗脱法测定30名受试者服用泮托拉唑前后人尿液内咖啡因5种主要代谢产物的相对含量,采用代谢物的比率分别评价人肝脏药物代谢酶CYP1A2、NAT2和XO活性的变化。结果:受试者用药前CYP1A2、NAT2和XO平均活性为3.37±1.22、0.50±0.09、0.49±0.09;服用泮托拉唑7 d后CYP1A2、NAT2和XO平均活性为3.50±1.23、0.48±0.12、0.48±0.13;服药前后3种酶活性没有显著性差异(P>0.05)。结论:泮托拉唑对人肝脏药物代谢酶CYP1A2、NAT2和XO活性无明显影响,泮托拉唑可能不会影响与之合用的需经CYP1A2、NAT2和XO代谢的药物临床疗效。     

质子泵抑制剂对药物代谢酶CYP1A2、NAT2的影响分析

目的 以健康人群作为研究对象,从代谢表型探讨质子泵抑制剂与药物代谢酶CYP1A2、NAT2的关系.方法 以咖啡因作为药物代谢酶CYP1A2、NAT2的探针药物,用反相高效液相色谱(RP-HPLC)方法测定尿液中咖啡因代谢物.结果 健康人群CYP1A2酶活性指标呈对数正态分布,NAT2酶活性活性指标呈两态分布.结论 以咖啡因探针法测定正常人肝脏药物代谢酶CYP1A2、NAT2活性的RP-HPLC梯度洗脱直接进样法,为国内深入开展CYP1A2、NAT2代谢酶的研究开拓了一种新方法.     

复方丹参滴丸对药物代谢酶CYP1A2，NAT2和XO活性影响的研究

目的探讨复方丹参滴丸对CYP1A2,NAT2和XO活性的影响,指导临床医师合理用药。方法以咖啡因作为探针药物,以HPLC测定受试者服用复方丹参滴丸前后尿液内咖啡因的5种主要代谢产物的相对含量,采用不同代谢物的比率分别评价 CYP1A2,NAT2和XO活性的变化。结果受试者用药前CYP1A2,NAT2和XO平均活性为4.20±1.54,0.36±0.12,0.33±0.05;服用复方丹参滴丸14 d后三者的平均活性为4.26±1.95,0.32±0.12,0.32±0.07;服用复方丹参滴丸28 d后三者的平均活性为4.35±1.26,0.30±0.11,0.31±0.04;服药14 d后CYP1A2,NAT2和XO活性无统计学差异;服药28 d后CYP1A2和NAT2活性无统计学差异,但XO的平均活性降低,且具有统计学差异。结论复方丹参滴丸对药物代谢酶CYP1A2和NAT2活性无明显影响。服用治疗剂量的复方丹参滴丸对XO活性具有抑制作用。     

银杏叶片对人药物代谢酶CYP1A2与NAT2活性的影响

（1. ［摘要］目的探讨银杏叶片对人肝脏药物代谢酶CYP1A2和N 乙酰基转移酶（NAT2）活性的影响,预测银杏叶片与常用药物的相互作用,指导临床合理用药。方法以咖啡因作为药物代谢酶CYP1A2、NAT2的探针药物,以反相高效液相梯度洗脱法测定30例受试者服用银杏叶前后尿液内咖啡因5种主要代谢物的相对含量,采用代谢物的比值分别评价人肝脏药物代谢酶CYP1A2、NAT2活性的变化。结果受试者服药前CYP1A2、NAT2平均活性分别为2.976±1.428,0.447±0.172;服用银杏叶片28 d后CYP1A2、NAT2平均活性分别为3.021±1.318,0.391±0.147;服药前后CYP1A2的活性差异无显著性,NAT2的活性差异有显著性。结论银杏叶片对人药物代谢酶CYP1A2活性无明显影响,但是对NAT2的活性有明显影响;银杏叶片可能不会影响其他经CYP1A2酶代谢的药物临床疗效,但是可以影响与之合用经NAT2代谢的药物临床疗效。     

HPLC直接进样测定咖啡因代谢物评价三种药物代谢酶活性

目的：建立测定尿中咖啡因的5种主要代谢物：5-乙酰氨基-6-甲酰氨基-3-甲基尿酸（AFMU）、1-甲基尿酸（1U）、1-甲基黄嘌呤（1X）、1，7-二甲基尿酸（17U）和1，7-二甲基黄嘌呤（17X）的高效液相色谱法，以评价N-乙酰基转移酶（NAT2）、细胞色素P450酶1A2（CYP1A2）和黄嘌呤氧化酶（XO）三种药物代谢酶的活性。方法：采用反相高效液相梯度洗脱法直接进样测定尿液内咖啡因代谢产物AFMU、1U、1X、17U和17X的相对含量，计算AFMU／（AFMU＋1X＋1U）、（AFMU＋1X＋1U）／17U和1U／（1X＋1U），绘制概率分布直方图，分别反映NAT2、CYP1A2和XO的活性。结果：NAT2活性呈两态分布，快、慢乙酰化代谢表型的临界点为0．26，CYP1A2和XO酶活性呈近似正态分布。结论：本方法简便、准确、快速，适合于尿中咖啡因代谢物的测定及NAT2、CYP1A2和XO等药物代谢酶活性的研究。     

咖啡因探针法测定正常人肝脏药物代谢酶CYP1A2活性

目的:建立咖啡因4种主要代谢物含量的测定方法,探讨咖啡因代谢物在药物代谢酶CYP1A2活性评价中的意义。方法:采用反相高效液相梯度洗脱法测定尿液内咖啡因代谢产物5—乙酰氨基—6—甲酰氨基—3—甲基尿酸(AFMU)、1—甲基尿酸(1U)、1—甲基黄嘌呤(1X)和1,7—二甲基尿酸(17U)的相对含量,计算代谢物比率(AFMU+1X+1U)/17U,绘制频数分布直方图,评价CYP1A2活性。结果:受试者代谢物比率平均值为4.27,呈正态分布。结论:本方法简便、准确、快速,适合于尿液中咖啡因代谢物的测定及CYP1A2活性的研究。     

测定咖啡因代谢物评价 N-乙酰转移酶、CYP1A2和黄嘌呤氧化酶活性

目的是对中国人N-乙酰化酶(NAT2)、CYP1A2酶和黄嘌呤氧化酶(XO)的活性进行分析。120名健康志愿者饮用3杯咖啡后于4～5h留尿,用HPLC方法测定尿中5种咖啡因主要代谢物浓度,即5-乙酰胺基-6-甲酰胺基-3-甲基尿嘧啶(AFMU)、1-甲基黄嘌呤(1X)、1-甲基尿酸(1U)、1,7-二甲基尿酸(17X)、1,7-二甲基黄嘌呤(17U)。其中N-乙酰化酶活性用AFMU/1X或AFMU/(AFMU+1X+1U)表示;CYP1A2酶活性指标采用(AFMU+1X+1U)/17X或AFMU+1X+1U)/17U;XO酶活性指标采用1U/1X或1U/(1X+1U)。结果表明,N-乙酰化酶活性呈两态分布,慢代谢者占16.7%,CYP1A2和XO酶活性呈对数正态分布,其代谢比值与国外文献报道一致。提示通过测定咖啡因代谢物比值,可以进行NAT2酶、CYP1A2酶和黄嘌呤氧化酶活性分析。     

奥美拉唑、兰索拉唑和泮托拉唑对黄嘌呤氧化酶活性的影响

目的:探讨奥美拉唑、兰索拉唑和泮托拉唑对药物代谢酶黄嘌呤氧化酶(XO)活性的影响,预测奥美拉唑、兰索拉唑和泮托拉唑与常用药物的相互作用,指导临床医师合理用药。方法:以咖啡因作为药物代谢酶XO的探针药物,以高效液相色谱法测定90名受试者分别服用奥美拉唑、兰索拉唑和泮托拉唑前后尿液内咖啡因2种主要代谢产物的相对含量,采用代谢物的比率评价药物代谢酶XO活性的变化。结果:服用奥美拉唑、兰索拉唑和泮托拉唑3种质子泵抑制剂前XO平均活性分别为(0.42±0.11),(0.37±0.13),(0.45±0.06);服药后活性分别为(0.40±0.09),(0.39±0.08),(0.43±0.08),服药前后药物代谢酶XO活性差异无显著性(P>0.05)。结论:短期内服用治疗剂量的奥美拉唑、兰索拉唑和泮托拉唑不会影响与之合用的需经XO代谢的药物疗效。     

振源胶囊对细胞色素P_(450)酶CYP1A2、CYP3A4、CYP2E1的影响

目的:研究振源胶囊对细胞色素P450酶CYP1A2、CYP3A4、CYP2E1的影响。方法:用Cocktail探针药物法,将Wistar大鼠随机分组,灌胃给予振源胶囊溶液,以生理盐水组为空白对照,诱导10d,于股动脉插管,注射给予3种探针药物咖啡因、氨苯砜、氯唑沙宗,通过高效液相色谱法检测各探针药物的代谢率来评价各组CYP1A2、CYP3A4、CYP2E1亚型酶的活性;药动学计算采用DAS2.0软件完成。结果:给予振源胶囊的大鼠,咖啡因代谢加快,半衰期缩短;氨苯砜代谢减慢,半衰期延长;氯唑沙宗半衰期与空白对照组比较无显著差异(P>0.05)。结论:振源胶囊对大鼠CYP1A2有诱导作用,对CYP3A4有抑制作用,对CYP2E1的作用不明显。     

Salivary clearance and urinary metabolic pattern of caffeine in healthy children and in pediatric patients with hepatocellular diseases

Measurement of salivary clearance and urinary metabolites of caffeine is an excellent noninvasive tool for assessing liver function, particularly the activity of cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT), and xanthine oxidase (XO). This study was undertaken to measure the clearance of caffeine using saliva as a biological fluid and to assess the activities of the above-mentioned enzymes in healthy children and pediatric patients with liver diseases using urinary molar ratios of different caffeine metabolites. The well-established two-sample saliva approach was used to measure the clearance of caffeine in nine pediatric patients with liver diseases (LD) and in nine healthy children. The caffeine metabolites were also measured in the urine of these subjects by high-performance liquid chromatography, and urinary molar ratios of 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (1X), 1-methyluric acid (1U), and 1,7-dimethyluric acid (17U) were employed to estimate the activities of CYP1A2, NAT, and XO. The caffeine salivary clearance and the percentage of the dose excreted in the form of various metabolites were significantly (p < 0.035) smaller in the LD patients than those in healthy children. The urinary molar ratio of [AFMU + 1U + 1X]/17U, which reflects the activity of CYP1A2, was also significantly (p < 0.0005) reduced in these patients. However, there were no significant differences between the two groups in the ratios of AFMU/1X and 1U/1X, which estimate the activities of NAT and XO, respectively. In conclusion, the data obtained suggest that liver disease in pediatric subjects significantly reduces the salivary clearance of caffeine and the activity of cytochrome P4501A2, but it has no impact on the activities of NAT and XO.     

The effect of Shoseiryuto,a traditional Japanese medicine,on cytochrome P450s, <Emphasis Type="Italic">N</Emphasis>-acetyltransferase 2 and xanthine oxidase,in extensive or intermediate metabolizers of CYP2D6

Objective Shoseiryuto (TJ-19) contains eight herbal components, including Ephedra sinica, and has been used for treating asthma and allergic rhinitis in Asian countries for several centuries. In this study, we investigated the potential herb–drug interaction of TJ-19 in healthy volunteers and attempted to ascertain whether or not the interaction might be affected by the cytochrome P450 (CYP) 2D6 genotype. Methods We assessed the effect of TJ-19 on the activities of CYP1A2, CYP2D6, CYP3A, xanthine oxidase (XO), and N-acetyltransferase 2 (NAT2) in 37 healthy subjects. The subject pool consisted of 19 extensive metabolizers (EMs) with CYP2D6*Wild/*Wild, and 18 intermediate metabolizers (IMs) with CYP2D6*10/*10. The baseline activities of five enzymes were ascertained by their respective urinary metabolic ratios from an 8-h urine sample, after an oral 150-mg and 30-mg dose of caffeine and dextromethorphan were administrated, respectively. Thereafter, the subjects received 4.5 g of TJ-19 twice daily for 7 days, and underwent the same phenotyping test on postdose day 7. Results The activities of all enzymes examined did not differ before or after the 7-day administration of TJ-19. Consequently, the influence of the CYP2D6 genotype on the herb–drug interaction remained unsolved. Conclusion Our results indicate that TJ-19 at the generally recommended dosage is unlikely to cause pharmacokinetic interaction with co-administered medications primarily dependent on the CYP1A2, CYP2D6, CYP3A, XO, and NAT2 pathways for elimination.     

Interaction of ibuprofen and probenecid with drug metabolizing enzyme phenotyping procedures using caffeine as the probe drug

AIMS: To examine the suspected inhibitory potential of the over-the-counter (OTC) drug ibuprofen on N-acetyltransferase 2 (NAT2) in vitro and in vivo and the possible implications for phenotyping procedures using caffeine as probe drug. METHODS: We first studied the inhibitory effect of ibuprofen on NAT2 in vitro, using human liver cytosol and sulfamethazine as substrate. In vivo 15 fast and 15 slow acetylating healthy volunteers were treated with a single dose of ibuprofen (800 mg) orally and phenotyped for NAT2, CYP1A2, and xanthine oxidase (XO) with caffeine as probe drug before and during drug treatment. Because of unexpected in vivo results with ibuprofen this study was repeated in 20 healthy volunteers with probenecid, a model substrate of renal organic anion transport (OAT). For phenotyping tests a urine sample was collected 6 h after caffeine (200 mg) intake. The caffeine metabolites acetyl-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (1MX), 1-methyluric acid (1MU), and 1,7-dimethyluric acid (17MU) were quantified by HPLC, and the corresponding metabolic ratios for CYP1A2, NAT2, and XO were then calculated. Genotyping for NAT2 was performed with standard PCR-RFLP methods. RESULTS: In vitro, with human liver cytosol an inhibition by ibuprofen of the acetylation of sulfamethazine with Ki values between 2.2 and 3.1 mm was observed. Surprisingly, in vivo a significant (P < 0.001) increase of the acetyl-6-formylamino-3-methyluracil/1-methylxanthine (AFMU/1MX) urinary ratio from 0.97 +/- 0.16 to 1.08 +/- 0.18 (95% CI on the difference 0.049, 0.170) was found, indicating an apparent elevation of NAT2 activity. In contrast, no change was observed for the ratios used for XO and CYP1A2. Because an induction of NAT2 could be excluded, an interaction of ibuprofen with the tubular secretion of some of the caffeine metabolites was assumed. To prove this assumption, the in vivo study was repeated with probenecid, a model substrate of the renal OAT system. Again, a prominent elevation of the AFMU/1MX ratio from 0.97 +/- 0.21 to 1.53 +/- 0.35 was found (P < 0.002; 95% CI on the difference 0.237, 0.876), but also the XO ratio 1MU/1MX was significantly (P < 0.0001) increased from 1.34 +/- 0.09 to 2.24 +/- 0.14 (95% CI on difference 0.735, 1.059) due to a reduction of 1MX excretion. CONCLUSIONS: Substrates of OAT interact with renal excretion of caffeine metabolites and may falsify NAT2 and XO phenotyping results. Other phenotyping procedures, which are based on urinary metabolic ratios, should also be validated in this respect, especially in patients under polymedication.     

Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities

Objectives: To evaluate the in vivo effect of xanthine oxidase (XO) inhibition by allopurinol on the determination of polymorphic N-acetyltransferase 2 (NAT2) and cytochrome P450 1A2 (CYP1A2) with urinary caffeine metabolic ratios. Methods: In an open, prospective study involving 21 healthy subjects (eight fast, 13 slow NAT2 acetylators) allopurinol (300 mg perday) was administered orally on trial days 1–8, followed by a wash-out period of 8 days. Urinary caffeine tests (200 mg caffeine p.o.) were performed repetitively. Urine was collected for 8 h and venous blood samples for the determination of allopurinol, oxypurinol and uric acid were drawn. The urinary caffeine metabolites 1-methyluric acid (1MU), 1-methylxanthine (1MX), 1,7-dimethyluric acid (17MU), 1,7-dimethylxanthine (17MX), 5-acetylamino-6-formylamino-3-methyluracil (AFMU), plasma allopurinol and oxypurinol were analysed using high-performance liquid chromatography (HPLC). Results: During XO inhibition by allopurinol, the formation of 1MU from 1MX and therefore the XO ratio 1MU/1MX decreased to 15.9 (1.2)% [mean with (SEM)] of baseline values (P < 0.005). The NAT2 ratio AFMU/1MX decreased likewise to 56.7 (6.3)% (P < 0.005). AFMU/(AFMU + 1MX + 1MU), an alternative NAT2 ratio, remained constant, but the CYP1A2 ratio (AFMU + 1MX + 1MU)/17MU, used to express CYP1A2 activity, transiently increased to 167 (13)% (P < 0.005). The NAT2 phenotype did not influence CYP1A2 and XO ratios or plasma oxypurinol pharmacokinetics. Conclusions: Several caffeine metabolic ratios are commonly used to express the activities of NAT2, CYP1A2 and XO both in healthy volunteers and in polymedicated patients, although their reliability has not been evaluated thoroughly during concurrent drug administration. The findings of this study suggest that NAT2 phenotyping should be performed using the ratio AFMU/(AFMU + 1MX + 1MU) if an XO inhibitor may be present. It also shows that the determination of CYP1A2 activity with caffeine as a metabolic probe is considerably altered under these conditions. Thus, concomitant drug administration may impair the robustness of multiple pathways of the complex caffeine test. This points to the need for alternative probes, designed to assess only the activity of a single enzyme because, in contrast to healthy volunteers, in patients known or unknown drug interactions may often be present. Received: 10 August 1998 / Accepted in revised form: 5 October 1998     

Differential alteration of drug-metabolizing enzyme activities after cyclophosphamide/adriamycin administration in breast cancer patients

Cyclophosphamide (CPA) and adriamycin (ADR) are widely used drugs for cancer chemotherapy. It has been reported that CPA and ADR singly or in combination could alter activities of a variety of drug-metabolizing enzymes in animals via multiple mechanisms. However, the effects of CPA/ADR on drug metabolism are largely unknown in human beings. Losartan metabolism has been suggested as a marker for determination of CYP2C9 activity. Caffeine is a commonly used probe to assess the metabolic activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO). The present study was designed to analyze the effects of CPA/ADR on these drug-metabolizing enzymes by using losartan and caffeine as probe drugs. A single oral dose of 25 mg losartan and a cup of instant coffee was given to 15 breast cancer patients on three occasions (before, and 2-4 h and 3 weeks after the adjuvant CPA/ADR chemotherapy [600 mg CPA/m2/day, 60 mg ADR/m2/day]). Losartan, caffeine and their metabolites were analyzed by using high-pressure liquid chromatography. When compared with baseline, CYP1A2 activity was increased by 20% and CYP2C9 activity was decreased by 315% 3 weeks after the administration of CPA/ADR chemotherapy (p = 0.05). The chemotherapy did not change the activities of CYP2A6, NAT2 or XO. CPA/ADR treatment caused a differential effect on drug-metabolizing enzyme activities, and this may contribute to predicting the efficacy and toxicity of chemotherapeutics, as well as understanding the drug-drug interactions.     

Genistein alters caffeine exposure in healthy female volunteers

Purpose

This study investigated the effect of 1?g genistein daily for 14?days on caffeine-based metrics of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6), N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO).

Methods

A single dose of 100?mg caffeine was administered once before and once on the last day of a 14-day treatment regime with 1?g genistein once daily to 18 healthy female volunteers. Urine and blood samples were collected up to 12 and 24?h, respectively, after each caffeine dose. Using high-performance liquid chromatography (HPLC), caffeine and 1,7-dimethylxanthine (17X) were quantified in plasma, whereas 17X, 1,7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), and 5-acetylamino-6-formylamine-3-methyluracil (AFMU) were quantified in urine. Urinary metabolite ratios were calculated to assess enzyme activities and compared between administrations using analysis of variance (ANOVA).

Results

Genistein decreased the urinary caffeine metabolite ratio used to assess CYP1A2 activity by 41% [90% confidence interval (CI) 28?C51%). The urinary ratio indicating XO activity decreased by 29% (90% CI 24?C32%), whereas urinary ratio for CYP2A6 activity increased by 47% (90% CI 29?C66%) after 2?weeks of genistein. The NAT2 urinary caffeine metabolite ratio did not change significantly.

Conclusions

Two weeks of intake of 1?g genistein daily led to decreases in CYP1A2 and XO activity and an increase in CYP2A6 activity, whereas NAT2 activity did not change in healthy Chinese female volunteers. Pharmacokinetics of other substrates of the enzymes investigated here may be influenced in a similar manner.     

Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females

AIMS: To investigate the influence of St. John's wort (SJW) on CYP3A4, CYP1A2, CYP2D6, N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO) activities in healthy males and females. METHODS: Eight males and eight females were treated with SJW extract (3 x 300 mg day(-1)) for 14 days. Assessment of CYP1A2, NAT2, XO, CYP2D6, and CYP3A4 activities was performed before and at the end of the study period, using caffeine, dextromethorphan, and endogenous cortisol as probes. The corresponding metabolic ratios measured were 17MX/137MX in saliva and (AFMU+1MX+1MU)/17MU in urine for CYP1A2, AFMU/1MX for NAT2, 1MU/1MX for XO, DOR/DMO for CYP2D6, 3MM/DMO and 6OHC/C for CYP3A4, all determined in urine. RESULTS: The ratios of the treatment to baseline values for CYP3A4 using cortisol as the probe were 1.5 [95% confidence interval (CI) 1.3, 1.9] for males, and 1.9 (1.1, 3.0) for females. The corresponding ratios using dextromethorphan as the probe for CYP2D6 were 0.9 (95% CI 0.5, 2.1) for males and 1.9 (1.3, 3.2) for females. For CYP1A2, a significant increase in the metabolic ratios was found only for females (ratio of values 1.2; 95% CI 1.1, 1.4). No influence of SJW on CYP2D6, NAT2, and XO activities was observed. CONCLUSIONS: An induction of CYP3A4 by SJW was confirmed. CYP1A2 appears to be induced by SJW only in females. The activities of CYP2D6, NAT2, and XO were not affected by SJW.     

A herbal-drug interaction study of keishi-bukuryo-gan, a traditional herbal preparation used for menopausal symptoms, in healthy female volunteers

Objectives Many patients use herbal medicines to relieve menopausal symptoms. Keishi‐bukuryo‐gan contains five herbal components, and has been used for treating hypermenorrhoea, dysmenorrhoea and menopausal symptoms in Asian countries. In this study, we investigated the potential herb–drug interactions of keishi‐bukuryo‐gan in healthy female subjects. Methods Thirty‐one healthy females (20–27 years) were studied to evaluate their baseline activity of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N‐acetyltransferase 2 (NAT2) based on the urinary metabolic indices of an 8‐h urine sample collected after a 150‐mg dose of caffeine and a 30‐mg dose of dextromethorphan, and also the urinary excretion ratio of 6β‐hydroxycortisol to cortisol. Thereafter, the subjects received 3.75 g of keishi‐bukuryo‐gan twice daily for seven days, and underwent the same tests on post‐dose day 7. Key findings The geometric mean phenotypic index for CYP1A2 significantly decreased by 16% on day 7 compared with the baseline (P = 0.026). Keishi‐bukuryo‐gan did not alter the indices for CYP2D6, CYP3A, XO and NAT2. Conclusions Keishi‐bukuryo‐gan may inhibit the activity of CYP1A2, which is predominantly involved in oestrogen metabolism. However, TJ‐25 is unlikely to participate in herb–drug interactions involving medications predominantly metabolized by CYP2D6, CYP3A, XO and NAT2.