- DDi vdi mot sDthuDc chi sau khi chuyen hoa mdi cotac dung hoac tang dQc tinh thi cam ling enzym lam tang tac dung hoac tang dQc tinh cua thuoc.
4. THAI TRU (elimination)
4.2.1. Bai tiet qua mgt
Nhirng thuoc co trong luong ph an til <300 thuong duoc bai tiet qua nude ti~u con nhirng thuoc co trong luong phan til cao hon thuong duoc bai tiet qua mat. Su v~n chuyen thuoc tu cac te bao gan vao mat duoc thuc hien theo co che khuech tan don thuan hoac van chuyen tich cue, Vi du cac chat mau (do phenol, bromosulfthalein), cac penicillin ... duoc bai tiet vao mat theo co che v~n chuyen tich cue, Cac chat co ban chat la base, cac thanh phan hiru co trung tinh co cac nhom ph an cue ciing duoc bai tiet qua mat. Cac sulfonamid, cloramphenicol va mot sO'khang sinh khac duoc bai tiet qua mat d nang dQco tac dung kim hoac diet khuan. Cac chat ua lipid (lipophilic), cac chat lien hop vdi acid glucuronic duoc bai tiet qua mat vdi sO'luong dang k~. Tu m~t cac chat nay duqc d6 vao rUQt,mQt ph~n chung se duqc tai hap thu d rUQtrai d6 vao gan t~o thanh chu ky gan- ruQt. (Cac san phftm glucuro lien hqp chi duqc tai hap thu sau khi da duqc thuy phan thanh chat ban d~u duoi anh hUdng clla enzym hydroxylase).
4.2.2. Bdi tietqua dich dq, ddy
MQt SO'thuO'Ctu mau co th~ qua niem m~c d~ day trd ve dich d~ day. Voi cac chat co ban chat la base yeu se co nang dQd dich d~ day cao hon nang dQd huyet tuong ngay ca khi dung dUdng tiem vi pH clla dich d~ day rat acid (1- 3),
con pH d huyet tuong hoi kiem (7,4). DO'ivoi nhung chat nay neu hling sO'phan ly cang IOn thi nang dQ clla no trong dich d~ day cang cao hon nang dQ trong huyet tuong. Vi v~y, khi ngQdQccac alcaloid bat k~ dung bling dudng nao ngudi ta v§.n thudng tien hanh rila d~ day.
4.2.3. Bdi tiet qua nUdcb(}t
MQt sO'alcaloid (quinin, atropin, strychnin v.v.), mQt sO'muO'ikim lo~i n?ng, paarcetamol, penicilin, tetracyclin, sulfamid, theophylin v.v. bai tiet qua nuoc b9t. Trong qua trinh bai tiet chung v§.nco th~ gay ra nhung tac d1,lngnhat dinh. Vi d1,lspiramycin bai tiet qua nuoc b9t co tac d1,lngchO'ngnhi~m khuftn khoang mi~ng.
4.3. Thai tru qua dliong ho h~p
DUdng ho hap la dUdng thai tru nhanh nhat dO'ivoi cac chat khi, cac chat long bay hoi nhu ether, cloroform, alcol, tinh d~u v.v... MQt sO'chat sau khi chuy~n hoa cilng duqc thai tru qua cac phe nang, vi d1,l cac d§.n chat alkylthiocyanat (co trong hanh, toi). St;i thai tru qua cac phe nang tht;ic hi~n theo co che khuech tan don thuAn. Muc dQ thai tru tang len khi thuO'Cit tan trong huyet tuong ho?c tang luu luqng mau toi ph6i. MQt sO'chat duqc bai tiet qua dich phe quan, anh hUdng den tinh chat clla dich phe quan. Vi d1,lnatri
benzoat khi bai tiet gay kiem hoa dich phe quan lam long thanh ph~n
mucopolysacarit do do d~ thai ra ngoai (tac d1,lnglong ddm).
Ngoai cac dUdng thai tru tren thuO'Ccon duqc thai tru qua sua m~ (alcol), tuyen rna hoi (d§.n chat arsen, muO'ikim lo~i n?ng v.v...), nuoc m~t (cac iodit, d§.nchat arsen, d§.nchat thuy ngan v.v...).
4.4.M<)tso thong so duco d<)nghoc lien quan de'n qua trinh thai tru 4.4.1. D9 thanh loc Cl (Clearance)
Do thanh loc (he so'thanh thai - Cl) cua cd thi dOl v{Jimot thuoc la thi tich mdu h~iJ,chuyet' tuang duacca thilog,i bo hoan toan thuoc i6 trong mot dan vi thai gian. Don vi bi~u thi d9 thanh 19Cla mU min hoac mU mini kg th~ trong. C6 th~ tinh d9 thanh 19Ctheo cac bi~u thuc sau:
CI= KeD =K, . Vd (10)
Cp
Ke:hang so t6c d9 thai tru =0, 693/ tl/2
Cp:nong d9 thuoc trong huyet tuong. Vd: th~ tich ph an b6
Trong truong hop thuoc phan b6 cao trong h6ng c~unhu labetalol, mot so' thuoo chong s5t ret v.v... d~ tranh sai so' khi tinh CI phai tinh theo n6ng d9 thuoc trong mau toan phan (Cb)chu kh6ng tinh theo n6ng d9 thu6c trong huyet tuong (Cp).
Hoac: CI= FD
AUeo00 (11)
F: sinh kha d\lng clla thu6c D: lieu dung
AUC: di~n tich duoi dUdng cong
D9 thanh 19Cclla cd th~ la tang d9 thanh 19Cclla cac cd quan trong d6 gan va th~n d6ng vai tro quan tr9ng nhat.
CI=Cigan+ Clth~n+ Clcdquankhac (12)
Cac gia tri ve d9 thanh 19Ctrong cac tai li~u tra cuu chinh la d9 thanh 19C clla cd th~ (tang d9 thanh 19Cclla cac cd quan) .
.
4.4.1.1. DC}thanh 19Ccua gan (Clgan)
DC}thanh 19Ccua gan ciIng nhzt dC}thanh 19ccua cac cd quan khac dOl v{Ji mC}tchat la thi tich mau hoiJ,chuyet tztdng dztr;Jcgan (hoiJ,ccd quan khac) log,ibo
hoan toan chat d6 trong mC}tddn vj thdi gian.
Cigan=Q.E
Q :luu IUQngmau qua gan E : h~ so'chiet tach clla gan
E = Cy -CR
Cy
Cy: n6ng d9 thu6c dmau vao gan (mau d9ng mlilch) CR: n6ng d(>thu6c dmau ra khoi gan (mau tinh mlilch)
(13)
Dua tren h~ so chiet tach cua gan nguoi ta chia thuoc thanh hai loai: loai thu nhat bao gam nhfing thuoc rna su loai tru cua chung phu thuoc chu yeu vao
luu hrong mau tdi gan. Loai nay thuong co de) thanh loc cao, h~ so chiet tach cao
(E>O,8) do do phan IOn thuoc bi chuyen hoa khi qua gan. Vi du lidocain,
propranolol v.v. Loai thu hai co de) thanh loc thap, h~ so chiet tach thap (E <
O~2)do hoat tinh cua enzym chuyen hoa thu6c d gan kern hoac do thuoc lien ket cao vdi protein huyet tuong. Vi du warfarin, diazepam v.v ...
4.4.1.2. fJ9thanh 19Ccua thtin. (Clthc!-,)
De)thanh loc cua than duoc tinh theo bi~u thuc sau:
Cl - Q.Cu
thi).n-~
p
(15)
Q: toc de)bai tiet nude ti~u
Cu:nang de)thuoc trong nude ti~u Cp: nang de)thuoc trong huyet tuong
Tir bi~u thuc (14) co th~ tinh duoc toc de)thai tru thuoc:
Ve= Q.Cu = Cl. C, (16)
Trong lam sang d~ danh gia chuc nang than nguoi ta co th~ dua vao de)thanh lQccua creatinin ne)isinh. Neu Clcreatinin<80mU min la suy th~n. Khi do neu:
CICreatinin> 50mLl min: suy th~n nh~
CICreatinin= 15 - 50mU min: suy th~n trung binh
CICreatinin::; 15mLl min: suy th~n n~ng
De)thanh lQc coy nghla rat IOn trong dieu trio Me)t thuoc co de)thanh lQc IOn se duqc thai tru nhanh. Khi biet d~ thanh lQcngudi ta co th~ tinh toan lieu duy tri d~giucho nang de)thuoc trong huyet tudng dtr~ng thai 6n dinh.
4.4.2. N6ng df)atrq,ng thcii on dinh (ess)
Nang de)d tr~ng thai 6n dinh (Steady state concentration) hay noi gQn l~i la nang de)6n dinh (co tac gia gQi la nang de)can b&ng) la nang de)trong huyet tudng d~t duqc khi toc de)hap thu va toc de)thai tru tudng dUdng.
4.4.2.1. Trong trztdng hc;tptruyin tlnh mg,ch lien tlj-c:
Css= KJ Cl= K/ Cl (17)
Ko: h&ng so toc de)tiem truyen
Ke: h&ng so t6c de)thai tru cua cd th~
4.4.2.2. Trang truimg hap dua thucc vaa co the'khong lien tuc (l<J,pdi liip lai qua
duiJng uorig, tiem b&pv.v...)
css=F.DI CLt (18)
Css: gia tri trung binh cua Css
F: sinh kha dung D: lieu dung CI: de)thanh 19c
t: khoang each thoi gian giua cac l~n dung thuoc