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- W4252149715 abstract "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." @default.
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- W4252149715 date "1997-05-01" @default.
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- W4252149715 title "PREDICTION OF THE THERAPEUTIC DOSE FOR BENZODIAZEPINE ANXIOLYTICS BASED ON RECEPTOR OCCUPANCY THEORY" @default.
- W4252149715 doi "https://doi.org/10.1002/(sici)1099-081x(199705)18:4<293::aid-bdd24>3.3.co;2-2" @default.
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