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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
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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