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11.
PREDICTION OF THE THERAPEUTIC DOSE FOR BENZODIAZEPINE ANXIOLYTICS BASED ON RECEPTOR OCCUPANCY THEORY
KIYOMI ITO AKIKO ASAKURA YASUHIKO YAMADA KOUICHI NAKAMURA YASUFUMI SAWADA TATSUJI IGA 《Biopharmaceutics & drug disposition》1997,18(4):293-303
Many benzodiazepines (BZPs) are now used as anxiolytics with nearly 200-fold variety of therapeutic doses. The variation of the doses of BZPs is due to differences both in their pharmacokinetics and in their receptor binding characteristics. The purpose of this study is to clarify the mechanism of the differences in therapeutic dose by retrospective analyses and to develop a system for the quantitative estimation of optimal doses of BZPs. The values of receptor dissociation constant (Kd), which indicates the binding affinity of each BZP at the receptor site, were obtained from a number of works based on in vitro binding experiments. The plasma unbound concentrations of the BZPs and their active metabolites were calculated using the reported values of their total plasma concentrations after average oral doses of the BZPs and the values of their plasma unbound fractions, which were also taken from the literature. There were log-linear relationships between the Kd values of BZPs and their average therapeutic doses or maximum plasma concentrations, but the correlation coefficients were relatively small (r >0·77). In contrast, a good log-linearity (r =0·96) was observed in the correlation between their Kd values and the effective plasma unbound concentrations considering the active metabolites. This finding indicates that the receptor occupancy after administration of therapeutic dose of BZPs is consistent (52·3±3·2%) among the BZPs. In this study, we also develop a possible system for estimating the appropriate doses of BZPs based on receptor occupancy theory. ©1997 by John Wiley & Sons, Ltd. 相似文献
12.
AKIKO T. UEDA M.D. HARUMIZU SAKURADA M.D. Ph.D. MITSUHIRO NISHIZAKI M.D. Ph.D. MASAYASU HIRAOKA M.D. Ph.D. 《Pacing and clinical electrophysiology : PACE》2010,33(11):e102-e105
We report a case of mirror‐image dextrocardia with antidromic atrioventricular reciprocating tachycardia via the Mahaim fiber. Using the noncontact mapping system, arborized ventricular insertion of the Mahaim fiber was identified and successfully ablated. (PACE 2010; e102–e105) 相似文献
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TOSHIRO NAGAI TAKASHI KANEKO HIROMI SHICHIJOU TAKAKO KARATO AKIKO MARUYAMA YUTAKA TSUCHIYA 《Pediatrics international》1993,35(5):404-408
A Japanese boy aged 2 years 11 months with late infantile metachromatic leukodystrophy underwent bone marrow transplantation (BMT) from his human leukocyte antigen (HLA) identical but mixed lymphocyte culture reactive father. Chimerism and increased arylsulfatase A activities of leukocytes had been observed with retarded progression of neurological deterioration during the first 3 months post-BMT. Graft rejection gradually occurred and donor cells were almost completely eliminated from the patient at 1 year after BMT. The process of neurodegeneration progressed clinically and neuroradiologically. Three possible reasons for the pathogenesis of graft rejection are: (i) T cell depletion of donor marrow cells as graft-versus-host disease (GVHD) prophylaxis; (ii) a slightly weak conditioning regimen; and (iii) a small number of marrow cells transplanted. It is stressed that as BMT is still a preliminary therapy for metachromatic leukodystrophy indications, conditioning, and GVHD prophylaxis for BMT should be considered individually. 相似文献
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SEIICHIRO SUGIMOTO md HIROAKI HOSHI md AKIKO SUGIMOTO md . TAKEKAZU OHI md SHIGERU MATSUKURA md KATUSHI WATANABE md 《Psychiatry and clinical neurosciences》1997,51(6):405-410
Abstract The purpose of this study is to find the correlation between middle latency auditory evoked potentials (MLAEP) and sound activated single photon emission computed tomography (SPECT) studies. This study was performed on six normal right-handed volunteers with a mean age of 35.2 ± 7.6 years, using the split-dose technique. First, a SPECT study was performed on subjects in blinded, awake and silent states. After bilateral ears were stimulated with a click sound, MLAEP and a second SPECT study were performed. Subtraction of the first SPECT from the second SPECT revealed a statistically significant increase of cerebral blood flow (CBF) in the bilateral superior temporal region. Bilateral Na amplitudes of MLAEP had a statistically significant and good correlation with the percentages of CBF changes in the bilateral superior temporal region. The superior temporal cerebral blood flow activation can be expressed by electrophysiological activation. Moreover, correlation during the left Na components and left frontal and occipital lobe are discussed. 相似文献
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HISAKAZU OHTANI HAJIME KOTAKI YASUFUMI SAWADA TATSUJI IGA 《The Journal of pharmacy and pharmacology》1997,49(4):458-462
The effects of epinastine hydrochloride and terfenadine on electrocardiographic (ECG) parameters in rats were investigated from a pharmacokinetic and pharmacodynamic perspective. Epinastine hydrochloride (1 or 3 mg kg?1 h?1) or terfenadine (5, 10 or 15 mg kg?1 h?1) was intravenously infused into rats anaesthetized with urethane and α-chloralose. The changes in the QT interval derived from limb lead II and the chest lead, heart rate and PR interval were analysed. The time-course of the plasma drug-concentration of each drug was also investigated. Terfenadine prolonged the QT interval in an infusion-rate-dependent manner; its EC50 value was 792–1039 ng mL?1. An obvious QT prolongation was, moreover, observed even at a plasma terfenadine concentration of 100–200 ng mL?1, which is clinically quite high, but might be achieved under a definite condition such as a restrained terfenadine metabolism. Terfenadine also induced PR prolongation and bradycardia in an infusion-rate dependent manner. Epinastine slightly increased the heart rate, but did not affect any of the other ECG parameters even at a plasma concentration of 400 ng mL?1, which is more than 10 times the maximum concentration attained after an ordinary dosage regimen in man. We conclude that epinastine might have an advantage over terfenadine in avoiding adverse electrocardiographic reactions. 相似文献
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YASUYUKI SASAKI AKIKO FURIHATA KAZUHIRO SUYAMA 《Pacing and clinical electrophysiology : PACE》1994,17(9):1477-1486
We compared signal-averaged electrocardiography (SAE), SAE mapping, and left ventricular catheter mapping in 60 patients with ischemic heart disease. Using the data obtained in patients with no fragmented electrograms (EE) in the left ventricle, the late potential was defined by SAE as a filtered QRS duration > 131 msec or a root mean square voltage < 16 μV for the last 40 msec of the QRS complex. SAE mapping was performed by recording the signal-averaged electrocardiogram at 48 sites on the body surface. With SAE mapping, the filtered QRS duration and the area in the last 20 msec of the QRS complex were significantly different between the patients with and without EEs. The late potential was defined by SAE mapping as a filtered QRS duration > 136 msec or an area < 28 μV.msec for the last 20 msec of the QRS complex. The sensitivity and specificity of detecting FEs were 46% and 88%, respectively, by the SAE filtered QRS criterion, while they were 66% and 88% by the root mean square criterion. In contrast, SAE mapping gave values of 66% and 92% by the filtered QRS criterion, as well as values of 100% and 92% by the area criterion. Thus, SAE mapping provided better detection of the EE and was more closely correlated with the results of catheter mapping, suggesting its potential for clinical application. 相似文献