• 検索結果がありません。

ON THE THREE-COMPARTMENT MODEL IN PHARMACOKINETICS FROM THE VIEWPOINT OF THE ALMOST-ONE PARAMETER HYPOTHESIS

N/A
N/A
Protected

Academic year: 2021

シェア "ON THE THREE-COMPARTMENT MODEL IN PHARMACOKINETICS FROM THE VIEWPOINT OF THE ALMOST-ONE PARAMETER HYPOTHESIS"

Copied!
5
0
0

読み込み中.... (全文を見る)

全文

(1)

     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.      .   .

273

(2)

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 by

REFERENCE

[1]  Masuyama, M. G Ogata, H.〔1987):Ashort note on the urinary excretion        process, TRU Mathemαties, 23−2, 269−272.

(3)

      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 TOKYO

(4)

276

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.」・・

(5)

we obtain three sets of prametric relations. 〔・。〕 ・・一刀㌢・、、.」一・、.k・ 〔・b〕、Σ・一・画・!、k.」・・、k.一ゴ㌧・一・・an・

〔・。) ・・一力たプちピ・、.k。

砲ere we define fomally that

(A・8) ・。=0・F。=ヱ・・ガ1・Fm 一 0・nd c・n,+ヱー0・      1・ikewise, we obtain another three sets of para皿etric relations.

〔・・。〕 ・・一・・輪.2硫.」一・、.W

〔・・b〕 ・・一・・婦・・ 2陶・。.ゴ・・ ! 2、古・.a…

〔・・。) ・・一・鯖 2硫.」−F2.,祠・

N°te that・」・Fゴ飢d 3ぴsati・fy id・ntical re1・ti・ns e・・ept・P・ssibly parameters with indices O orπ∼.      Ib ・・d Ilb・・e a・y・t・m・f・imult飢・・u・equ・ti・n・in F・ぬi・h h・・th・ following solutions.

(A・9〕 F㌍・9’.ヱ/・、・トヱ・2・…・m−1・

     Hence there holds a vectorial relation 〔A・10〕[5ヱ・52・・… Sm]−R[・1・・2・…・・m]≠[・2/・1・・3/・1・…・・ン・ヱ・0]・ ぬich皿eans that the straight lin・Zi・in・id・nt with・fix・d p・int r・2/・ヱ・α3/・ヱ・

…・・

刀E1・oノ・      Now let us cons ider the difference of two characteristic equations for two different persons, say (・…)r・、一・、り・m’一ヱーr・2−・、りzm−2・…・r−・M−2r・m−、一・m.、りz+       m一ヱ        ー5 り=0.       .      r一力        r5        m    m      It follows that (…2) ・、・M一ヱー・2・M−2・・…r−・ノm−2・m.、z≠r−・)m一ヱ・m−・。・r 〔…3〕 ・M一ヱー・Z−2・・、zM“3−…・・(一 om−2Fm.2・≠r−・ノm一ヱFm.ゴ・. which is the equation of伽.力co㎜on roots among persons. In other words, there remains only one characteristic root which represents the individuality.      We n°te that th・param・t・ic relati・ns l。・1。・Ila・nd IIc are directly derivable from the equation (A.12),or (A.13),e.g. 〔…4) ・、.、−r・2/・ノー2r・3/・、〔、2−2・、・

参照

関連したドキュメント

In particular, we consider a reverse Lee decomposition for the deformation gra- dient and we choose an appropriate state space in which one of the variables, characterizing the

Maria Cecilia Zanardi, São Paulo State University (UNESP), Guaratinguetá, 12516-410 São Paulo,

The main problem upon which most of the geometric topology is based is that of classifying and comparing the various supplementary structures that can be imposed on a

Then it follows immediately from a suitable version of “Hensel’s Lemma” [cf., e.g., the argument of [4], Lemma 2.1] that S may be obtained, as the notation suggests, as the m A

Using the batch Markovian arrival process, the formulas for the average number of losses in a finite time interval and the stationary loss ratio are shown.. In addition,

[Mag3] , Painlev´ e-type differential equations for the recurrence coefficients of semi- classical orthogonal polynomials, J. Zaslavsky , Asymptotic expansions of ratios of

We study the classical invariant theory of the B´ ezoutiant R(A, B) of a pair of binary forms A, B.. We also describe a ‘generic reduc- tion formula’ which recovers B from R(A, B)

For X-valued vector functions the Dinculeanu integral with respect to a σ-additive scalar measure on P (see Note 1) is the same as the Bochner integral and hence the Dinculeanu