The number of deaths caused by asthma attacks has been decreasing in recent years due to the widespread use of inhaled corticosteroid (ICS). However, in some poor adherence cases, severe asthma ...attacks have occurred and resulted in emergency visits and hospitalization. To date, there is no detailed examination report to evaluate the influence of temporary discontinuation of therapeutic drugs on a respiratory function test. Therefore, this clinical study was undertaken. The clinical trial was performed at Showa University Clinical Research Institute for Clinical Pharmacology and Therapeutics from April to July in 2014, with 15 healthy subjects and 20 bronchial asthma patients enrolled in the study. For the respiratory function test FVC, FEV1.0, FEV1.0%, %FEV1.0, V25, V50, PEF were measured. The tests were conducted twice on different days and each parameter was analyzed comparatively. The use of long-acting inhaled β2 receptor agonists (LABA), anti-leukotriene agents, and anti-allergic agents for the asthma patients were discontinued in accordance with the study design before their second visit to the study site. The test result in healthy subjects showed a significant increase in FEV1.0%, V50 and V25 on their second visit, while in the asthma patients a marked decrease in PEF was seen after stopping the medication. The decrease in PEF was particularly larger in patients using ICS and LABA compared to the non-users. This result indicates a decline of PEF in the patients with bronchial asthma due to the withdrawal of corresponding treatment even without the exacerbation of the subjective symptom. In conclusion, patient education regarding the improvement of adherence will be a very important for asthma control.
Oxidative stress is one of causes of atherosclerosis due to lifestyle-related diseases. Recently easy methods have been developed to measure oxidative stress using Diacron-Reactive Oxygen Metabolites ...(d-ROMs) test and antioxidant potential using Biological Antioxidant Potential (BAP) test were developed. Low-density lipoprotein (LDL) is changed to oxidized (Ox) LDL by oxidative stress in blood. It is important that the antioxidant potential is effective for oxidative stress in vivo. However, the association between oxidative stress and lipid in blood has not been clarified. In this study, we investigated the association between oxidative stress and lipid in blood as a factor of atherosclerosis. There were 149 subjects (98 males and 51 females) who underwent a health checkup examination in a company. We measured d-ROMs, BAP and OxLDL. We defined that the BAP/d-ROMs ratio is the corrected ratio. We supposed the corrected ratio of > 12.5 to be “no oxidative stress state” and the corrected ratio of ≦ 12.5 to be “oxidative stress state”. Ox LDL, triglyceride (TG) and apolipoproteinB (ApoB) in “oxidative stress state” were higher than those in the “no oxidative stress state”. High density lipoprotein (HDL) in “oxidative stress state” was lower than that in “no oxidative stress state”. There was a positive correlation between d-ROMs test and OxLDL (R=0.376, p<0.0001), and a negative correlation between BAP test and TG (R=-0.503, p<0.0001). There was no correlation between d-ROMs and TG. There was a negative correlation between BAP and OxLDL (R=-0.167, p=0.0413) and it was insignificant compared with the correlation between d-ROMs and OxLDL. We derived low levels of BAP (BAP≦3500) and normal levels of BAP (BAP>3500). There was a strongly negative correlation between BAP and TG in low levels of BAP (R=-0.585, p<0.0001). However, there was no correlation between BAP and TG in normal levels of BAP. In this study, it was clarified that the oxidative stress was related to OxLDL and there was a negative correlation between antioxidant potential and TG. Easy methods for measuring oxidative stress such as d-ROMs and BAP will be useful for the evaluation of atherosclerosis risk and the subsequent prevention of cardiovascular diseases.
In Japan, many medical doctors utilize Kampo medicine in their daily practice in combination with Western medicine. However, there have been few reports investigating the drug-drug interactions via ...cytochrome P450 (CYP) between these medicines. In our previous study, long-term administration of anchusan increased the serum midazolam (MDZ) concentrations in rats and humans, suggesting the inhibition of intestinal CYP3A likely caused by the metabolites of anchusan constituents. To clarify the property of this effect, we conducted a short-term anchusan treatment study in human and investigated its effect on MDZ metabolism. The open-label, fixed-sequence, 2 period study was performed in 12 healthy men who were divided into two groups A and B. Each subject was administered 7.5mg MDZ orally as a control trial prior to the anchusan treatments. MDZ was administered again after either 2 hours (Group A) or 16 hours (Group B) of three times 2.5g anchusan treatments. Serial blood samples were collected over 8 hours after each MDZ dose. The serum MDZ concentrations were analyzed by HPLC and its pharmacokinetic parameters were determined. The visual analogue scale (VAS) was used for the estimation of the sedative effect. The short-term anchusan treatment did not show any remarkable change in MDZ pharmacokinetics (AUC0-8, Cmax and t1/2), although a statistically significant but minor decrease of AUC0-8 was observed after anchusan treatment in Group B. The VAS score showed a similar value between before and after anchusan treatment in both groups. The results showed that short-term (3 times) anchusan treatment did not inhibit MDZ pharmacokinetics and pharmacological effect, when MDZ was administered 2 or 16 hours after the last anchusan dose. CYP3A-mediated drug interaction caused by short-term anchusan does not occur under this condition.
