AI CNG VE

SINH DC HOC
( BIOPHARMACEUTICS )
GSTS. L Quan
Nghim
 1.C s hnh thanh mon SDH
Cac d kien quan sat lien quan en hieu
qua tr lieu cua thuoc.

Bot cam thao vi strychnin sulfat hap phu

73%
vi atropin sulfat hap phu
41%.
 1.C s hnh thanh mon SDH
tac dung tr lieu khac nhau khi s dung mot loai
dc pham (cung mot dang thuoc ,cung ham lng
dc chat,cung at cac tieu chuan kiem nghiem,
cung ng s dung) trong cac trng hp nh:
-biet dc cua hai nha san xuat khac nhau(khac ve ta
dc, ky thuat san xuat).
-san pham t nhng lo san xuat khac nhau (khac
nhau ve ieu kien san xuat).
- oi tng s dung va ieu kien s dung khac nhau
 1.C s hnh thanh mon SDH
-Vien digoxin 0,25mg vi ngi s dung khac nhau( nong o
thuoc trong huyet tng 0,5 ng/ml so vi 2ng/ml)
-Thay calcium sulfat dihydrat bang lactose trong vien phenytoin
gay ngo oc
Y thc vai tro cua :
-thanh phan trong cong thc
-ta dc
-dang thuoc
-ng s dung
-ngi s dung
Anh hng en ket qua tr lieu
Nghien cu cac yeu to nay hnh thanh mon SDH
 Khai niem SDH

a- SDH la mon khoa hoc

- Nghien cu anh hng cua thanh phan va
cach bao che en tac dung sinh hoc cua
dang thuoc
( WAGNER .1961)
 Khai niem SDH
b- SDH nghien cu cac yeu to anh hng
en:
-S phong thch va hoa tan DC vao moi
trng dch the
-S van chuyen thuoc en ni hap thu va i
qua mang sinh hoc (PROUDFOOT)
 Khai niem SDH
c- SDH nghien cu anh hng cua tnh chat
ly hoa, dang thuoc, ng dung thuoc en
toc o va mc o hap thu thuoc.
Nh vay, SDH nghien cu:
-s bao ve DC trong dang thuoc
-s phong thch DC t dang thuoc
-toc o hoa tan thuoc ni hap thu
-s hap thu qua mang
-ng dung thuoc.
(Leon Shargel, Andre B.
Phan loai cac yeu to anh hng en
SKDoi tng cua SDH.
a- YEU TO DC HOC:
- Tnh chat ly hoa, c hoc cua DC:
kch thc tieu phan, o tan, dang ket tinh
- Thanh phan ta dc
- Dang bao che
- Ky thuat ieu che, trang thiet b s
dung

SINH DC HOC BAO CHE

Phan loai cac yeu to anh hng en
SKDoi tng cua SDH.
b- Yeu to sinh hoc:
- Yeu to ca the
- ng s dung
- ieu kien s dung
- Tnh trang sinh ly
- Tnh trang benh ly
SINH DC HOC LAM SANG
 Y ngha cua nghien cu SDH
- Xac nh ng dung thuoc tot nhat
- Thanh phan va dang thuoc toi u nhat.
- La chon, s dung thuoc ung an, hp ly,
hieu qua.
- Phat trien cac he thong tr lieu mi.

MUC TIEU CUA SDH

 Sinh kha dung cua thuoc
La ac tnh ca dng thuc ch toc o va mc
o cua:
-thanh phan hoat tnh,
-goc hoat tnh
-chat chuyen hoa co hoat tnh
-c hap thu vao tuan hoan chung va san
sang ni tac ong
 Sinh kha dung cua thuoc
+oi vi dc pham khong nham hap thu
vao mau, SKD c o lng bang cac
tieu ch phan anh toc o va mc o ca
- Thanh phan co hoat tnh
- Gc hoat tnh
- Cht chuyn ha c hot tnh
san sang ni tac ong
 Sinh kha dung cua thuoc
-SKD c xac nh bang cac thong so dc
ong hoc:
+ Tmax ( toc o hap thu )
+ Cmax ( mc o va toc o hap thu)
+ AUC ( mc o hap thu)
( AREA UNDER THE CURVE )
-Thuoc tiem tnh mach c xem la co SKD
100%.
-Cac ng s dung khac (uong, at di li,
at trc trang ) cho SKD thap hn.
 o th nong o thuoc trong huyet tng
Nong o
mcg/ml theo thi gian
(a) ( o th nong o mau )

MTC
Cmax

Khoang tr lieu
Cng o tac
ong
MEC

AUC
Khoang tac
ong

t1 t(max) t2 Thi gian

(h)
 Phan loai SKD
SKD tuyet oi
* T le thuoc nguyen ven c hap thu.
* Cong thc:
(AUCT )abs
F % = x 100
(AUCT)IV

( AUCT )abs x DIV

F% = x 100
(AUCT )IV x Dabs
 PHAN LOAI SKD

F% : SKD tuyet oi (%)

(AUCT)abs: Dien tch di ng cong toan the
cua dang th (g/l.h; g/ml.h. )
(AUCT)IV: Dien tch di ng cong toan the
cua dang tiem tnh mach.
DIV, Dabs : La lieu cua dang tiem tnh mach
va dang th c s dung t mot ng
khac.
 PHAN LOAI SKD

SKD tng oi:

SKD tng oi c xac nh bang cach -
lap t le gia dang th so vi dang chuan
(t mot dung dch nc a c biet la hap
thu tot)
SKD so sanh
-so vi mot che pham thng mai co hieu
qua lam sang tot a c tn nhiem.
* Cong thc:
(AUCT )test
F% = x 100
( AUCT )standard

F% : SKD tng oi (%)

(AUCT)test : Dien tch di ng cong toan
the cua dang th
(AUCT)standard : Dien tch di ng cong toan
the cua dang lam chuan
 (AUCT )test X Dstandard
F% = x 100
( AUCT )standard X Dtest

Dstandard, Dtest : la lieu cua dang chuan va lieu

cua dang th.
o th nong o thuoc trong huyet tng theo thi gian
(o th nong o mau)
Nong o
mcg/ml
(a)

MTC
Cmax

Khoang tr lieu
Cng o tac
ong
MEC

AUC
Khoang tac
ong

t1 t(max) t2 Thi gian

(h)
Nong o

C3

C2

C4

C1

C5

C6

1 2 3 4 ... t
gi

 Cong thc tnh AUC
*Phng phap toan hoc

AUC0 = C. dt

*Phng phap thc nghiem tnh tong dien tch cac

hnh thang.
CO + C1 C1 + C2
AUC0t = (t1 t0) + ( t2 t1 )
+
2 2

n
AUC 0t = Ci + Ci + 1 (t t )
------------- i+ 1 i
i=1 2
 Cn
AUC t =
Ke

Cn :Nong o thuoc thi iem lay mau

cuoi cung (t)
Ke: Hang so toc o thai tr cua dc chat

n v AUC : g/l.h; g/ml.h; ng/ml.h; g .h .ml-1

n
Ci Ci 1 Cn
AUC O (ti 1 ti )
i 1 2 Ke
 5. Cac khai niem tng ng.

Tng ng dc phm/bo ch
Th phm bo ch
Tng ng sinh hoc
Tng ng tr lieu
DP thay the tr lieu
 Tng ng dc phm/tng
ng bo ch
(pharmaceutical equivalents)
*khi 2 dc pham giong nhau
hoat chat
ham lng
dang thuoc
ng s dung
*am bao tieu chuan chat lng
*san xuat tuan thu GMP
*co the khac nhau: ta dc ,hnh dang, tuoi tho,
c che phong thch, nhan
* hieu qua tr lieu ???
 Th phm bo ch (pharmaceutical
alternatives)
*la dp co goc hoat tnh giong nhau nh vay
khac dang muoi , ester, phc
( vd: tetracyclin clorhidrat va tetracyclin
phosphat)
*khac nhau ve dang thuoc
( vd: vien nen vien nang)
*khac nhau ve ham lng
*khac nhau ve he thong
(vd: phong thch keo dai - tc thi)
 Tng ng sinh hoc
(bioequivalents)

hai che pham T dc hoc hoac DP thay the

dc hoc la TSH khi :

1.SKD khong khac nhau co y ngha thong ke (

xac nh trong ieu kien tng t )
*mc khac biet c chap nhan :
nho hn hoac bang 20%
 Tng ng sinh hoc
(bioequivalents)

2.mc o hap thu (AUC, Cmax ) khong khac

nhau; s khac nhau ve toc o hap thu( tmax)
do co y, c ghi trong nhan, khong quan
trong vi viec at nong o tr lieu trong c the
trng hp man tnh va c xem khong co y
ngha lam sang.
 Tng ng sinh hoc
(bioequivalents)

*y ngha TSH:
+so sanh theo tieu ch dc ong hoc
+TSH: tng ng tr lieu
+khong TSH: xem xet lam sang ?
 Tng ng tr lieu
*hai che pham cha hoat chat giong nhau
cho ket qua tr lieu va co phan ng phu
tiem an nh nhau theo ieu kien c
ghi tren nhan
* co the khac nhau: mau, mui, hnh dang,
tuoi tho, nhan
 Dc pham thay the tr lieu
*DP cha hoat chat khac nhau c ch
nh cho muc tieu tr lieu va lam sang
giong nhau
*la DP co DC khac nhau nhng cung
nhom dc ly
vd : ibuprofen - aspirin
 CAC PHA ONG HOC CUA
THUOC TRONG C THE
Pha sinh dc hoc
( biopharmaceutical phase)
Pha dc ong hoc

( pharmacokinetic phase)
Pha dc lc hoc

( pharmacodynamic phase )
 PHA SINH DC HOC
PHA DC LC HOC

PHA DC ONG HOC

DANG THUOC

PHONG THCH NGAN NGOAI BIEN

(MO, TE BAO...)
TIEU PHAN
DC CHAT - S NHAY CAM
PHAN BO - SO LNG
Hoa tan
IV
NGAN TRUNG TAM
IM
DC CHAT TAN Dang THU THE PHAN NG
TRONG DCH THE GAN
Dang
DC LY
NG TIEU HOA t do ket
hp

CHUYEN HOA

BAI TIET TAI HAP THU

- Nc tieu - Than
- Mat - Gan ruot
- Nc bot
HANG RAO SINH HOC
HANG RAO ENZYM

HNH 3. S O TRNH BAY CAC HNH THC A THUOC VAO C THE

DIEN BIEN SO PHAN CUA DC VA PHAN NG DC LY.
Cac pha ong hoc cua thuoc trong c
the
* PHA SDH:
Qua trnh t khi dung thuoc en khi DC c
hap thu vao c the
Cac qua trnh thay oi tuy dang thuoc, cau
truc
Vd: -thuoc vien nen: LDA
-Dung dch nc : A
Y ngha cua cac qua trnh oi vi SKD va
bao che dang thuoc???
Cac pha ong hoc cua thuoc trong c
the

Pha SDH tieu bieu cua vien nen

DANG THUOC TIEU PHAN DC DC HOA TAN DC TRONG MAU
L D A

* RA * HOA TAN( D) *
HAP THU( A)
* PHONG THCH(L)
Cac pha ong hoc cua thuoc trong c
the
PHA DC ONG HOC
HAP THU (A )
PHAN BO (D )
CHUYEN HOA ( M )

THAI TR (E )
PHA DC LC HOC
 7. Cac yeu to anh hng en SKD
cua thuoc.
7.1. Cac yeu to dc hoc.
Cac yeu to anh hng en cac qua trnh phong
thch, hoa tan, hap thu pha sinh dc hoc eu co
anh hng en sinh kha dung cua thuoc.
Cac ac tnh ly hoa c hoc cua dc chat.

Kch thc tieu phan chat ran(KTTP).

Kch thc tieu phan co lien quan en dien tch be
mat chat ran, do o anh hng en toc o hoa tan.
 Phng trnh toc o hoa tan trong c
the (Nerst Bruner).
dm DA
= ( CS C )
dt h
m: Lng thuoc hoa tan tai ni hap thu.
dm
: Toc o hoa tan
dt
D: He so khuech tan cua phan t thuoc trong moi trng
dch the.
A: Dien tch be mat tiep xuc vi moi trng dch the
h: Be day lp khuech tan xung quanh tieu phan chat tan.
Cs: Nong o bao hoa cua thuoc trong moi trng dch the.
C: Nong o thuoc trong khoi dch the mot thi iem.
 Cac yeu to dc hoc
V du: Vi Griseofulvin, khi giam KTTP t 10
m en 2,7m lam tang gan gap oi lng
thuoc c hap thu ngi (Atkinson va Cs
1962).
Do o lieu 250mg Griseofulvin bot sieu mn
(ultra micronisee) cho nong o thuoc trong
mau tng ng lieu 500 mg bot mn
(micronisee).
Nong o trong huyet tng cua griseofulvine sau khi
dung lieu duy nhat cua dang micronisee va ultra
micronisee.
A: griseofulvin ultra micronisee 500mg.
B: griseofulvin ultra micronisee 250mg
C: griseofulvin micronisee 500mg.

1 A
B
0.8
mic ro g a m/ml

C
0.6

0.4

0.2

0
0 2 4 6 8 10 12 24
Gi
 Cac yeu to dc hoc.
Dang ket tinh va dang vo nh hnh
Dang vo nh hnh co o tan cao hn dang
ket tinh, co the anh hng en SKD. V du:
novobiocin, chloramphenicol, insulin kem.
Vi insulin kem, ngi ta ket hp 3 phan
dang vo nh hnh va 7 phan dang ket tinh
e ieu che che pham co tac dung keo dai
(30 gi).
 Cac yeu to dc hoc.
Cac dang a hnh
Dc chat co the co nhieu dang ket tinh khac
nhau va co o tan, toc o tan khac nhau. V
du: chloramphenicol cho nong o dang B
trong mau cao gap 10 lan dang A.
Dang hydrat hoa
Thng th dang khan tan nhanh hn dang
ngam nc (hydrat). V du Ampicilin cho
lng thuoc trong huyet tng cao hn dang
Ampicillin trihydrat
 7.1. Cac yeu to dc hoc
He so phan bo dau - nc
La t le tan trong dau so vi tan trong nc cua dc
chat.Dc chat co tnh tan trong dau cao va phu
hp de c hap thu qua mang (cau tao chu yeu la
lipid).
Kha nang ion hoa cua phan t
Cac dang ion hoa de tan trong nc, khong tan trong
lipid, nen s hap thu qua mang rat kem.
Cau truc muoi va este
Cau truc muoi b ion hoa lam dc chat de tan trong
nc nhng kho hap thu.
Cau truc este de b thuy giai hoac kho hoa tan, la m
anh hng en SKD cua thuoc.
 7.1. Cac yeu to dc hoc
S tao phc va hap thu dc chat
Cac tac nhan trong cong thc bao che, trong
moi trng sinh hoc co the tao phc hoac
hap phu dc chat, do o co the lam cham
hoac lam giam t le hap thu
 7.1. Cac yeu to dc hoc
7.1.3. Cac yeu to thuoc dang bao che va ky thuat
bao che
Moi dang bao che co ac iem rieng v thanh phan
cong thc, cau truc, ky thuat bao che co anh hng
en SKD cua thuoc. SKD cua dc chat co khuynh
hng giam theo th t:

Dung dch nc > Hon dch nc > Nang thuoc >

Vien nen > Vien bao.

Ngoai ra trang thiet b cung anh hng en cau truc

ly hoa cua dang thuoc, do o anh hng enSKD.
 7.2. Cac yeu to sinh hoc.
Cac yeu to sinh hoc co anh hng quan
trong en SKD cua thuoc, do o het sc lu
y khi s dung thuoc. Cac yeu to tieu bieu
gom co:
ng s dung thuoc

( uong ,tiem, at tren da)

Tuoi (tre em, trng thanh, gia ).

Tnh trang co thai.

The trong.
 Cac yeu to benh ly
Gia cac c the khoe manh a co s ap ng khac
nhau oi vi thuoc, cac c the b benh s khac
biet cang ro net hn.
Can lu y cac benh ly co anh hng en s hap
thu, chuyen hoa, thai tr cua thuoc.
V du:
S suy giam chc nang gan than
s chuyen hoa bai tiet, cac thuoc dung chung
ac biet khi s dung cac thuoc co khoang tr lieu
hep, phai co che o giam sat tr lieu oi vi tng ca
nhan benh nhan.
 Kiem tra kien thc
Thuat ng sinh kha dung cua thuoc e
cap en t le thuoc en
a- ruot non b- da day
c- tuan hoan chung d- gan
e- than

-ap an: c
 Cac thong so dc ong e anh gia sinh kha dung
cua thuoc la:
a- nong o toi a, thi gian ban thai, hang so toc o
thai tr
b- thi gian ban thai, thi gian at nong o toi a,
hang so toc o hap thu
c- nong o toi a, thi gian at nong o toi a, dien
tch di ng cong toan the
d- nong o trung bnh trong huyet tng, dien tch di
ng cong, thi gian ban thai
e-hang so toc o hap thu, dien tch di ng cong,
hang so toc o thai tr

-ap an : c
Nong o toi a trong huyet tng tng ng:
a- thi iem co tac ong dc ly toi a
b- thi iem co s hap thu va thai tr tng
ng
c- thi iem co nong o toi a cua dc chat
trong nc tieu
d- thi gian can thiet e hau het dc chat
c hap thu t he trang v
e- thi iem thuoc bat au b chuyen hoa

-ap an:b
 Thi gian at nong o toi a cua thuoc trong
huyet tng la ch th tng oi cua:
a. s hap thu
b. s phan bo
c. s chuyen hoa
d. s thai tr
e.s bien oi sinh hoc

-ap an: a
 Dien tch di ng cong ai dien cho:
a- so lng thuoc c thanh thai bi than
b- thi gian ban thai cua thuoc
c- so lng thuoc nguyen ven c bai tiet
d- so lng thuoc hap thu
e- so lng thuoc trong dang thuoc

ap an: d
 S khac nhau ve sinh kha dung thng
thay oi vi thuoc s dung theo ng
a- di da
b- tiem tnh mach
c- uong
d- at di li
e- tiem bap tht

-ap an: c
 Tm sinh kha dung tuyet oi cua vien nang vi lieu
100mg co AUC la 20 mg/ dl. h va dang tiem tnh
mach vi lieu 100mg co AUC la 25mg/dl . h
a- 20%
b- 40%
c- 80%
d- 125%
e- 200%

-apan:c
 Tnh sinh kha dung tuyet oi cua vien nen
theo d lieu sau
Dang thuoc Lieu AUC ( g/ml. h )
Vien nen 100mg uong 20
Dung dch 100mg uong 30
Tiem 50 mg IV 40
a. 25%
b. 38%
c. 50%
d. 60%
e. 90%
-ap an:a
 Tnh sinh kha dung tng oi cua vien nen
theo d lieu sau
Dang thuoc Lieu AUC ( g/ml. h
)
Vien nen uong 100mg 20
Dung dch nc uong 100mg 25
Dung dch tiem IV 50 mg 40
a. 50%
b. 80%
c. 62,5%
d. 25%
e. 40%
-ap an:b
 Hai dc pham cha cung loai hoat chat co
dien tch di ng cong bang nhau: a.cung
cap lng dc chat nh nhau cho c the v
the la tng ng sinh hoc
b.cung cap lng dc chat nh nhau cho c
the nhng khong nhat thiet la tng ng
sinh hoc
c.la tng ng sinh hoc theo nh ngha
d.la tng ng sinh hoc khi ap ng tieu
chuan cua dc ien
e.la tng ng sinh hoc khi ca hai ap ng
tieu chuan o hoa tan

ap an:b
 Thuoc dung theo ng nao khong lien quan
en qua trnh hap thu
I Uong
II- Tiem bap
III Tiem tnh mach
a. ch I
b. ch III
c. ch I, II
d. ch II, III
e. ca I, II, III

- ap an:b
 . Cac dang thuoc c xep th t co sinh kha dung
kem dan
a- dung dch nc, vien nang, vien nen, bot, vien bao
, hon dch
b- vien nang, vien nen, vien bao, bot, hon dch, dung
dch nc
c- dung dch nc, hon dch, bot, vien nang, vien nen,
vien bao
d- hon dch, dung dch nc, bot, vien nang, vien bao,
vien nen
e- dung dch nc, hon dch, vien nang, bot, vien bao,
vien nen

-ap an: c