1991 Fiscal Year Final Research Report Summary
DEVELOPMENT OF A NEW THEORY FOR ESTIMATING PHARMACOKINETIC AND PHARMACODYNAMIC PARAMETERS OF NEUROMUSCULAR BLOCKING AGENTS.
| Project/Area Number |
02807143
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | TOKYO UNIVERSITY |
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Principal Investigator |
YAJIMA Choku TOKYO UNIVERSITY HOSPITAL,DEPARTMENT OF ANESTHESIOLOGY,ASSISTANT, 医学部, 助手 (20191108)
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| Co-Investigator(Kenkyū-buntansha) |
HANAOKA Kazuo TOKYO UNIVERSITY HOSPITAL,DEPARTMENT OF ANESTHESIOLOGY,PROFESSOR, 医学部, 教授 (80010403)
SUGAI Naosuke TOKYO UNIVERSITY HOSPITAL,DEPARTMENT OF ANESTHESIOLOGY,LECTURER, 医学部, 講師 (10010563)
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| Project Period (FY) |
1990 – 1991
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| Keywords | MUSCLE RELAXANTS / PHARMACOKINETICS / PHARMACODYNAMICS / PLASMA CONCENTRATION / SINGLE TWITCH / MONITOR / SHEINER'S MODEL / DIGITAL FILTER |
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| Research Abstract |
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)
where
l_0=control twitch height
delta=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>・C
delta''=delta/1+zeta(1/beta-k_<eo>+zeta/alpha-k_<eo>), zeta=A/B
C=k_<eo>-beta, V_d^<e*c>=(1+zeta)V_d
gamma ; slope factor, k_<eo> ; the rate constant from the effect compartment to outside
V_d ; cetral compartment volume, V_d^<e*t> ; extrapolated distribution volume
D ; initial dose, beta ; elimination rate constant, C^SS_50 ; the blood concentration that cause
C^SS_50 ; the blood concentration that causes 50% of the maximal response
A=gammalogdelta', A'=gammalogdelta, B=gamma, B'=gammabeta
Using 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)
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