Objective: To assess the efficacy of antihypertensive drugs, the time structure and autonomic nervous activity were calculated from 24-hour systolic blood pressure (24SBP) data in hypertensive patients.
Design and Method: Fifty-six patients with hypertension were treated with cilnidipine (10 mg once a day) or nifedipine-L (Nd-L, 20 mg twice a day) for 4.9±2.3 months. The 24SBP and electrocardiogram were recorded every 30 min before and after drug administration. The periodic structure of 24SBP was analyzed by the maximum entropy method (MEM). The fluctuation index (FI) of 24SBP given by the standard deviation of the differences from observed to best fittied SBP values was newly introduced to evaluate the 24-hour variability of SBP. The maximum speed of rise in SBP (maxΔSBP) and low frequency (LF) /high frequency (HF) power ratio from the heart rate variability in the 3 hrs after rise were also measured.
Results: The responders on anti-hypertensive therapy with cilnidipine (n=16) and Nd-L (n=17) were analyzed. The circadian rhythm during cilnidipine seemed to be normal. After the fall in BP, FI was decreased in cilnidipine from 1.09 to 0.94, but FI was increased in Nd-L responders from 0.91 to 0.98. The maxΔSBP was reduced in both cilnidipine and Nd-L responders. LF/HF became significantly lower in cilnidipine (2.5 to 2.0), but it rose in Nd-L responders from 2.2 to 2.8.
Conclusions: The FI can be considered as an index to assess the baro-reflex sensitivity throughout the day. The change in the time structure of circadian rhythm during the treatment is thought to be a means to evaluate the efficacy of anti-hypertensive therapy.

抄録全体を表示

To evaluate the loading regimen of teicoplanin, the total concentration of teicoplanin (C₂₄) and free teicoplanin concentrations (C_24free) in serum were measured 24 hrs after the start of therapy.
Thirty-eight points of blood samples from 35 patients were obtained after the intravenous loading of teicoplanin (200 or 400 mg per dose, every 12 hrs). Twelve patients received 200 mg of teicoplanin twice a day with a loading time interval of 12 hrs (400 mg/day group), and others received 400 mg twice a day, every 12 hrs (800 mg/day group). The acquired C₂₄ was 4.4±1.7μg/mL (mean±SD) in the 400 mg/day group and 8.9±3.7μJug/mL in the 800 mg/day group.C_24free was 0.7±0.17μg/mL in the 400 mg group and 1.3±0.17 μg/mL in the 800 mg group.C₂₄ and C_24free showed large variations among patients, and most of them remained at inadequate levels for the therapy when C₂₄>10, μg/mL or C_24free>1.56, μg/mL were set asthe target ranges. C_24free was well correlated with the body weight-adjusted loading dose (y=0.075x, r²=0.85). Although, C₂₄ showed a weak correlation (y=0.505x, r²= 0.28). This result was not affected by the renal function.
Therefore, it is suggested that for the clinical dosing schedules of teicoplanin, loading 10 mg/kg twice a day every 12 hrs should be an adequate amount for a loading dose. In addition, a maintenance dose, with the amount modulated according to the renal function of each patient, should be administered when necessary.

抄録全体を表示

The effects of controlled release nifedipine (nifedipine CR) on heart rate and the autonomic nervous system were investigated over a 12-week administration period in 19 patients with ischemic heart disease (17 males and 2 females, mean age 64 years) using spectral analysis of heart rate variability. No notable changes were found in the treatment period compared to the pre-treatment period in the low frequency (LF) or high frequency (HF) spectra or in the LF/HF ratio obtained from Holter monitor recording. The HF component is an index of vagal activity, while the LF component is an index of sympathetic activity with vagal modulation. The LF/HF ratio is thus considered to reflect sympathetic modulation. The results of spectral analysis of heart rate variability showed that nifedipine CR did not enhance sympathetic nervous activity, nor reduce vagal activity, indicating that nifedipine CR does not affect the autonomic nervous system. In addition, the drug had no effect on heart rate. An increase in heart rate and changes in the autonomic nervous system are negative factors associated with short-acting nifedipine in the long-term prognosis. The results of this study show that these adverse factors can be avoided by the use of a controlled release system.
The data therefore suggest that the nifedipine CR tablet (Adalat ^® CR tablet) is clinically more favorable than former nifedipine formulations, owing to the decreased load on the heart.

抄録全体を表示

According to Good Clinical Practice, any notification of safety information to the regulatory authorities during clinical trials/post-marketing clinical studies must be immediately reported to medical institutions. However, sequential reporting of each individual case has been a major burden for both the sponsor and the medical institutions, and it has caused various problems. Based on an analysis of such problems associated with the current reporting system and discussion with representatives from medical institutions as well, we propose the following procedures and format for improved reporting.
Safety information is classified into three categories according to the significance on clinical trials/ post-marketing clinical studies and the time frame for regulatory reporting: 1) Individual safety information requiring immediate reporting, 2) Individual safety information requiring prompt reporting (e.g. within one month), 3) Accumulated safety information requiring periodical reporting (approximately every three months).
These proposals are expected to facilitate accurate and timely transfer of important information, to promote the safety of clinical subjects, and to reduce a significant amount of the workload on both the sponsor and medical institutions.

抄録全体を表示

Clinical research coordinators (CRC) are now considered to be indispensable specialists in performing clinical trials, though CRC as a medical profession was only recently introduced to Japan. As the situation of clinical trials in Japan is different from that overseas such as in the United States, where the CRC system was originally developed, Japanese CRCs may face a different set of problems than those overseas. It is necessary precisely understand the present status of CRCs and the problems in establishing an educational program. Thus, we surveyed the status and problems of Japanese CRCs by a questionnaire. The question-naires were sent to 243 institutes, which are known to conduct clinical trials, and 215 replies were collected from 84 institutes. Approximately 60% of CRCs work full time, and the rest have an additional position. Their medical education backgrounds were: pharmacists (43%), nurses (38%), medical technicians (13%) and other bachelor degrees. While experience as CRC itself is short, most CRCs have a long experience in their own medical field. More than 80% of CRCs assist doctors in gaining informed consent. CRCs are faced a variety of difficulties in daily practice, and the difficulties differ, depending on their own medical background. Accordingly, several types of optional courses should be recommended for developing CRC educational programs in Japan.

抄録全体を表示