DEVELOPMENT OF A NEW THEORY FOR ESTIMATING PHARMACOKINETIC AND PHARMACODYNAMIC PARAMETERS OF NEUROMUSCULAR BLOCKING AGENTS.

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We developped new equations for obtaining hparmacodynamic and pharmacokinetic parameters of non-depolarizing muscle relaxants without measuring blood levels of these drugs. We applied these new equations to 46 clinical cases. Consequently we found that these equations could describe the onset process of neuromuscular relaxant agents, but that during the recovery phase these equatins needed some modifications because the constant parameter's value had been changed by chaging initial dose.Assumming two compartment model and Sheiner's model, the plasma level (C) of a muscle relaxant and the twitch height (1) follows next equations.C(t)=Ae^<-alphat>+Be^<-betat>(alpha>beta) ・・・・・(1)log(l_0-l/l)=gammalogdelta+gammalog(zetae^<-alphat>-e^<-keot>/k^<eo>-alpha+e^<-st>-e^<k-keot>/k_<eo>-beta/zeta+1 ・・・・・(2)wherel_0=control twitch heightdelta=k_<eo>・D/C^SS_50・V_d, delta'=delta/(1+zeta) (k_<eo>-beta) k_<eo>・D/C^SS_50・V_d^<e*c>・Cdelta''=delta/1+zeta(1/beta-k_<eo>+zeta/alpha-k_<eo>), zeta=A/BC=k_<eo>-beta, V_d^<e*c>=(1+zeta)V_dgamma ; slope factor, k_<eo> ; the rate constant from the effect compartment to outsideV_d ; cetral compartment volume, V_d^<e*t> ; extrapolated distribution volumeD ; initial dose, beta ; elimination rate constant, C^SS_50 ; the blood concentration that causeC^SS_50 ; the blood concentration that causes 50% of the maximal responseA=gammalogdelta', A'=gammalogdelta, B=gamma, B'=gammabetaUsing hyposethis that exp (-x)=1-x(x=0) and exp (-x)*0(x*) to equation (1) and (2), we derived two equations as follow.(]SY.encircled].[)[Onset phase log(l<@D20@>D2-l/l)=gammalogdelta+gammalog t ・・・・・(3)(]SY.encircledW.[)Recovery phase log(l<@D20@>D2-l/l)=gammalogdelta'-gammabetat+gammalog(1-e<@D1c・t@>D1) ・・・・・(5)