[Show abstract][Hide abstract] 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 6β-hydroxycortisol to cortisol. Thereafter, the volunteers received 3.75 g of seijo-bofu-to twice daily for seven 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 herb-drug interactions involving medications predominantly metabolized by CYP3A, CYP2D6, N-acetyltransferase 2 or xanthine oxidase. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: 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.
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 3.75g of keishi-bukuryo-gan twice daily for seven days, and underwent the same tests on post-dose day 7.
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.
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. K
[Show abstract][Hide abstract] ABSTRACT: Although the interaction between selective serotonin reuptake inhibitors (SSRIs) and other drugs is important in the treatment of depression, there have been few studies of SSRIs concerning transporter-mediated interactions in humans. The objective of this study was to evaluate the in vivo effects of commonly used SSRIs on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate.Twelve healthy volunteers (3 females and 9 males) were enrolled in this study. Each subject received a 60-mg dose of fexofenadine orally at baseline. Afterward, they were randomly assigned to receive 3 treatments with a 60-mg dose of fexofenadine after a 7-day treatment with fluvoxamine (50 mg/d), paroxetine (20 mg/d), or sertraline (50 mg/d), with 2-week intervals between the agents.Fluvoxamine pretreatment significantly increased the maximum plasma concentration, the area under the concentration time curves, and the 24-hour urinary fexofenadine excretion by 66% (P = 0.004), 78% (P = 0.029), and 78% (P < 0.001), respectively, without prolonging its elimination half-life. Paroxetine extended the elimination half-life of fexofenadine by 45% (P = 0.042), and it increased the 24-hour urinary fexofenadine excretion by 55% (P = 0.002). Sertraline did not alter any of the pharmacokinetic parameters of fexofenadine.This is the first report of the different effects of 3 commonly used SSRIs on fexofenadine pharmacokinetics in humans. Our 7-day, repeated-dose clinical study in healthy volunteers indicates that fluvoxamine and paroxetine, but not sertraline, may impact the patient exposure to fexofenadine, which is likely the result of P-glycoprotein inhibition in the small intestine and/or the liver.
No preview · Article · Apr 2012 · Journal of clinical psychopharmacology
[Show abstract][Hide abstract] ABSTRACT: The goal of pharmacogenetics is to deliver safe and effective drug therapy. Genetic polymorphisms in cytochrome P450 (CYP) enzyme genes are implicated in the inter-individual variability in pharmacokinetics of anti-epileptic drugs (AEDs). However, the clinical impact of CYP polymorphisms on AED therapy remains controversial. Previous studies have shown that the defective CYP2C9 alleles affect the required dose of phenytoin and the risk of its toxicity. We have reported that the CYP2C19-deficient genotype is associated with the serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the clinical efficacy of clobazam therapy. We determined also the influence of polymorphisms in CYP genes on the population pharmacokinetic parameters of AEDs using a non-linear mixed effect modeling program, which enables us to define relevant genetic factors together with other factors, and the magnitude of the effect on variation in pharmacokinetics in patients. The defective alleles of CYP2C9 and CYP2C19 were found to have significant effects on the inter-individual differences in clearance of phenobarbital and zonisamide, respectively. Based on these recent findings, we discuss the clinical significance of AED dose adjustment according to both genetic and non-genetic factors that affect CYP activity.
Full-text · Article · Jan 2010 · Epilepsy & Seizure