ON THE THREB−CCMPARTMENT MODEI、 IN PHARMACOKINETI CS
FROu THE VIEWPOINT OF THE雌)ST−ONE.Pma妊汀ER HYPOTHESIS
Mbtosal)uro MASUYAMA (Rece ived August 28, 1987) Let O r古ノ be the concentration of a drug in blood.カ hours after its ad皿inistration・Then according to the thlree−compartment mode1, we.have 〔1) 0「tノ=・1卿←λlt)チ・2卿「一λ2tノチ・3・UP「一λ3tノ・砲e「e・ゴ孤dλゴa「e c°nstants f°「ト1・2・3・F・㎝thi・w・ de「iv・adiff…nce
equation 『(2) oの醐一Short ・ 2hノ’子Qんατ柵一Rhcrt)一・・
hbeing a given constant, where we set (3〕 3㌍・‘OP(・・λlh)≠earp「一λ2hノ+ ・upr一λ3砿 Qh 一・UPトイλ戸λ2川・・鋤一rλ2 +・3川・卿卜r恒λヱノhl, Rh=earp [一 rλヱ≠λ2+λ3川・ λユ ≠ λ2≠λ3≠ λi is assumed・ The characteristic equation for this difference equation is given by〔4) z3−・〆・鰭一Rh・一・・
Let the parameters fbr the i−th sUbj ect be indexed by i. We may omit i and/or h, if there is no fear of・ confusion. N㎝,if the almost一㎝e parameter hypothesis is valid in this mode1, pOlnts(Shi. Qhi⊃ Rhi) are almost on one straight.1ine(5) 「Shi一万/・h = 「Qhi一β∂/βバ玩一〇h・ ・
where Ah・Bh・σh・・h ・nd Bh ar・ c・n・t・nt・ind・p・nd・nt・f i・Th・liP・passeS th・・㎎h・fiX・d p・int「Ah・Bh・0∂・nd it・di・e・ti・n i・giv・n by「・h・βh・力・ Replacing h by 2h in the equation (5),we obtain (6) 「S2hi−A2hノ/・2h・=rQ2hi 一 B2hノ/β2h = R2hi 一(72h・Since there exist algebraic relations. . .
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274
M.MASUYAMA
(・) ・、h’.一・h2−2Qh. Q、h−eh2−2SA・h。…R、h
we ca皿d6rive the fbilowing parametric relations: 2=R
h. (10) (11〕 曲ich shows that the point one pa「amete「Rhi・ On the other hand, let the characteristic equations of any two different subj ects (k/ and rゴノ be〔・・〕 93−・㎞み脇一㌔一・.rm−・・rゴノ.
舳おs㎝ing that騙≠%・we・bt・血’
(・3) ・h・2 一・hZ≠・一・,
which is the ・quati・n・f t・・.・・㎜・・…t・・H・・ceβゐ/・h ・ndヱ/・カare the s皿 amd the product of these two co㎜on roots respectively: Since the size of salgl)1e at hand [1] is too small to verify the various relations given above, we show only the linear relation 〔10) in Fig. 1. In this exa珂ple O(t/ denotes the urinary excretion rate, but not the concentration 加。s . in blood. V包1ues at t=6.5 are estlmated by the method of quadratic 血・・rP…ti・n,・・垣9・b・erv・ti・n・at・t−4.5.5.5、・・d 2h「s.・・i。 p。。b。b・y because of this that the fitting is not satisfactory.(・) ・2㌍・h2.β、h・ Bh2−2・h。
Ah ’α力(7h=β〆・h・Bh 一β碗=ヱ/・h・ A2h ’・2乃02バβ2〆・2h・B2h一β2hq2h =ヱ/・2h・ The vectorial relation ’ (9) [Ah・ Bh・ Ch]一[β〆・h・ヱ/・h・o]・eh[・h・βh・ヱ] tells u・th・t th・1ine(5〕i・麺・id・・t with th・fiX・d p・i・t rβh/・h・ヱ/・h・のand its di「ecti㎝i・para11・1 t・th・vect・r[・h・ Bh・ヱ]・ It follows from 〔5〕 and (8〕 that Sh=・hRh≠βV・h… d Qh 一 BhRh +1/・h… [Sh・Qh・ Rh]=[触力・ユ/・h・o]’+ Rh[・h・βh・ヱ]・ r5ハz∂θ}zi, Rhi/ for the i−th sUbj ect is detemined byREFERENCE
[1] Masuyama, M. G Ogata, H.〔1987):Ashort note on the urinary excretion process, TRU Mathemαties, 23−2, 269−272.3 . lt 3 2 1 0
−4 −3 −2 −1 0. 1%
Q五 1 0 −1 ● −2−4 −3 −2 −1 0 1㌦
Fig.1 The appendix was (;hecked by Dr. S. Kuriki, to whom the author is gratefuユ. DEPAR㎜T OF APPLIED MAT旺MAT工CS SCIENCE UNIVERSITY OF TOKYO276
M.MASUYAMA
鍵 The m−coMI)artment model under the one parameter hypothe『is. Let the difference equation for the m−compartment model be〔A・1) 0「t≠mhノーShlC「t・m一ヱh)・Sh2C「t・m−2hノー…
・r−・ノm−1・hrm.。Crt・hノ・(一・ノ㌦・r・)一・・ L where h is a given constant. Its characteristic equation is given by (・・2〕 aM 一・んノーヱ・5h、・M−2−・・『≠(一・ノm一ヱ%.、)・≠r−・ノ㌦一・・ぬe「etheゴーth「°°t is give晦%=⑳一λゴんノ・We set Sh・=ヱ・
Uhder the one−parameter hypothesis the point(A・3〕 「Shヱi・Sh2i・.…・,Sha) 「Z−1・2・…・・ゾ
for the i−th person is incident with a straight line Z, i.e. there are 2m pa「孤ete「s`and・」・which a「e independent°fいuch that
(A・4) 「5カビρ/・1=「Sh2i 一 A2ノ/・2=…=「Sh rm.ヱ)i−Am.∂/・m.1 =%ガAm・「・m=1ノ・ That is to say the line Z is incident with a fixed point (Aヱ3 423 … 」 Am) and i・para11・1 t・afix・d vect・r[・1・・2・…・・m]・ We may omit index, or indices, if there is no fear of misunderstanding. ’We set 囁 、(A・5) 輪R・εゴ=・ノ≠F♂・ぬe「e㌃Aゴー・協f°「」=ヱ・2・…・
m−13 and Rm= 0・ . 『 Wg replq・・hi・〔A・1〕by・2h・・nd. f・・m n…n・par・・p・ter・Uith i・d・x 2疏11 be indexell by 2.. ・hen・・ince・・h・v・・2.ゴー玩2・・etti…−t2・…b・… (・・6) r・m−・!一ヱ・・㌶一2−…・r−・m・il) (・m +・、tM“1+・…Smノ ー・M 一・、.、zm−1・・,.、zm−2−…・r−・ノm・、.m・…ce…n・ti……三。・坤・y・y…6・b…nre…i・…f・…ypes・
〔1) ・、バ・・一・・た々・」・、k.ゴ,m.2k、。。。、
(・・) ・、.,m.k戸・・一力陶・ 2、沸.」伽・2k・・
Ifノη is even, then these two equations coincide with each other, when m=2k. However, if m is odd, the second equation succeeds the first one. R・p・ese・ting 52. k in tw・way・a・aqu・drati・f皿・ti・n・f R= Ri・i…〔・・7) ・,ズ・2〆・F2.k 〔・・t・th・…、.m−・。㌦・h・nce・R、.−R2)
一・・一・酢・」…ゴ〃・2、.♂…,k.」・・we obtain three sets of prametric relations. 〔・。〕 ・・一刀㌢・、、.」一・、.k・ 〔・b〕、Σ・一・画・!、k.」・・、k.一ゴ㌧・一・・an・