I CNG V

SINH DC HC
Trn Vn Thnh

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 Khi nim

Sinh dc hc (SDH) l mt mn khoa hc

nghin cu s lin quan gia tc dng sinh hc
ca thuc v tnh cht l ha ca dng bo ch.

Thut ng tnh cht l ha ca dng bo ch

bao gm c im l ha ca c h thng phc
tp gm hot cht, t dc, cu trc v s hnh
thnh dng thuc di tc ng ca k thut,
cng ngh, trang thit b. => SDH bo ch

Tc dng sinh hc ca thuc l kt qu tng hp

ca cc yu t dc cht, dng thuc, ng s
dng thuc v cc yu t sinh l, bnh lca
c th ngi dng thuc. => SDH lm sng 2
 ngha nghin cu SDH

SDH nghin cu nh hng ca cc yu t l

ha, k thut bo ch, sinh l c th n tc
dng ca thuc nhm hng n vic to ra
dng thuc tt nht, cch dng thuc c hiu
qu nht, t tc dng khng mong mun nht.

SDH l c s pht trin dc phm vi nhng

tnh nng v c im mi.

SDH gip ngi thy thuc c c s k n

dng thuc ng n nht, bit phi hp thuc
mt cch khoa hc, k c phi hp vi ch n
ung, la chn thuc, cho liu ph hp vi tng
bnh nhn. 3
 Khi nim sinh kh dng

SINH KH DNG

SKD ca thuc l c tnh ch tc v mc ca

thnh phn hot tnh, gc hot tnh v cht chuyn ha
c hot tnh c hp thu vo tun hon chung v sn
sng ni tc ng. Phn liu thuc c hp thu
nguyn vn gi l liu kh dng.

TC - CNG - TRNG

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 Khi nim sinh kh dng

SINH KH DNG

TC - CNG - TRNG

3 thng s
Tmax
Cmax
AUC (din tch di ng cong)

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 Khi nim sinh kh dng

SINH KH DNG

SKD ca thuc l c tnh ch tc v mc ca

thnh phn hot tnh, gc hot tnh v cht chuyn ha
c hot tnh c hp thu vo tun hon chung v sn
sng ni tc ng.

i vi cht khng hp thu vo mu, SKD c o lng

bng cc tiu ch phn nh tc v mc m thnh
phn c hot tnh hoc nhm hot tnh sn sng ni tc
ng.

C hai loi SKD: tuyt i v tng i

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 Sinh kh dng tuyt i

SKD tuyt i l t l thuc nguyn vn so vi liu dng c hp thu:

F: SKD tuyt i (%)

(AUCT)abs: din tch di ng cong ton th ca dng th (n v mcg/l.h)

(AUCT)IV: din tch di ng cong ton th ca dng tim tnh mch

Nu dng khc liu cng thc c iu chnh

DIV, DABS: liu ca dng tim tnh mch v dng th c s dng t mt ng hp

thu khc.
SKD tuyt i cho php nh gi nh hng ca ng s dng trn hiu qa
sinh hc. 7
 Sinh kh dng tng i

SKD tng i : trng hp dc cht khng th s dng ng tim tnh

mch, ngi ta dng SKD tng i.

SKD tng i c xc nh bng cch lp t l gia dng th so vi dng

chun thng l mt dung dch nc c bit l hp thu tt hoc so vi
mt ch phm thng mi (trng hp SKD so snh) c hiu qu lm sng tt
c tn nhim.`

(AUCT) TEST x D STANDARD

F = x 100
(AUCT) STANDARD x D TEST

DSTANDARD: l liu ca dng chun

DTEST: l liu ca dng th

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 Sinh kh dng tng i

ngha:

Nhng thuc c SKD > 50% c coi l tt khi dng theo ng ung.

Nhng thuc c SKD > 80% th c th coi kh nng hp thu ca thuc qua
ng ung tng ng vi ng tim v nhng trng hp ny ch c
tim trong trng hp bnh nhn khng th ung c.

SKD tng i hay c dng nh gi ch phm mi hoc ch phm xin

ng k lu hnh vi 1 ch phm c uy tn trn th trng. Nu t l ny t
80-120% th c th coi 2 ch phm thuc tng ng nhau v c th thay
th nhau trong iu tr.

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1. Tm SKD tuyt i ca vin nang c liu 100mg c AUC l
20mg/dl.h v dng tim tnh mch vi liu 100mg c AUC l
25 mg/dl.h.

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2. Tm SKD tuyt i ca vin nn nh sau:

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3. Tm SKD tng i ca vin nn nh sau:

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 Cc khi nim tng ng

Tung ng dc hc (tng ng bo ch)

L cc ch phm cng dng bo ch, cng hm lng v loi

dc cht, cng ng s dng, c sn xut tun theo GMP
v t cc tiu chun cht lng quy nh, c th khc nhau v
t dc, hnh dng, tui th, c ch phng thch, nhn Cc
thuc tng ng bo ch c th c hiu qu tr liu ging
nhau hoc khc nhau.

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 Cc khi nim tng ng

Thay th dc hc

L cc dc phm c gc hot tnh ging nhau nh vy c th:

Khc nhau dng mui, ester, phcV d: tetracyclin

clohydrat v tetracyclin phosphat

Khc nhau v dng thuc. V d: vin nn v vin nang.

Khc nhau v hm lng. V d: vin paracetamol 325 mg v

500 mg.

Khc nhau v h thng. V d: dng phng thch ko di v dng

phng thch tc thi.
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 Cc khi nim tng ng

Tng ng sinh hc

L cc ch phm tng ng dc hc hoc thay th dc

hc c SKD ging nhau, nh vy l hai ch phm c tmax,
Cmax, AUC khng khc nhau c ngha thng k (mc khc
bit c chp nhn khng qu 20%).

Ch phm tng ng sinh hc hoc c th c xem l c

hiu qu tr liu tng ng.
Trng hp mc hp thu (AUC, Cmax) khng khc nhau, s
khc nhau v tc hp thu (tmax) do c , c ghi trong
nhn, khng quan trng vi vic t nng tr liu trong c th
trng hp bnh mn tnh v c xem khng c ngha lm
sng, vn c chp nhn tng ng sinh hc.

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 Cc khi nim tng ng

Tng ng sinh hc

Nng thuc trong huyt tng theo thi gian sau

khi dng liu duy nht ca 320mg Valsartan.

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 Cc khi nim tng ng

Tng ng tr liu

L cc ch phm cha cng loi, cng hm lng hot cht, cho

kt qu tr liu v c phn ng ph tim n nh nhau, theo iu
kin c ghi trn nhn, c th khc nhau v mu, mi, hnh
dng, tui th, nhn so snh tng ng tr liu, hai ch
phm phi tng ng sinh hc.

Thay th tr liu

L cc ch phm cha hot cht khc nhau c ch nh cho

mc tiu tr liu lm sng ging nhau (v d: ibuprofen v
aspirin).

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 Pha sinh dc hc

Bao gm cc qu trnh t khi dng thuc n khi dc cht

c hp thu vo c th. Ty dng thuc v ng s dng,
pha SDH c th gm cc qu trnh khc nhau.

V d: vi vin nn, pha SDH gm:

Qu trnh r (gii phng dc cht).

Qu trnh ha tan.

Qu trnh hp thu.

i vi dung dch nc khng c qu trnh r v ha tan m

dc cht sn sng hp thu. SDH nghin cu cc qu trnh
trong pha SDH v nh hng ca n n SKD ca thuc.
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 Pha dc ng hc dc lc hc

Pha dc ng hc

Bao gm cc qu trnh hp thu, phn b, chuyn ha, thi tr.

Mn dc ng hc nghin cu cc qu trnh ca pha dc
ng hc.

Pha dc lc hc

Bao gm cc qu trnh thuc kt hp vi th th dc l gy

tc ng sinh hc v thu c hiu qu iu tr. Mn dc lc
hc nghin cu cc ng thi ny.

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 Cc yu t nh hng SKD thuc dc cht

Kch thc tiu phn cht rn

Nng trong huyt tng ca Griseofulvin sau khi dng liu

duy nht ca dng bt
A Siu mn 500mg
B Siu mn 250mg
C Bt mn 500mg
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 Cc yu t nh hng SKD thuc dc cht

Dng kt tinh v v nh hnh

Dng v nh hnh c tan cao hn dng kt tinh
(Chloramphenicol, Insulin km)

Dng a hnh
Dc cht c th c nhiu dng kt tinh khc nhau, c tan
v tc tan khc nhau. V d Chloramphenicol c nng
dng bta trong mu cao gp 10 ln dng alpha.

Dng hydrat ha
Thng dng khan tan nhanh hn dng ngm nc (hydrat).

H s phn b du nc
Dc cht tan trong du cao hn trong nc vi mt t l
nht nh ph hp d hp thu do mng t bo ch yu l lipid.
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 Cc yu t nh hng SKD thuc dc cht

Kh nng ion ha ca phn t

Cc dng ion ha d tan trong nc, khng tan trong lipid,
nn s hp thu qua mng rt km.

Cu trc mui v este

Cu trc mui d ion ha lm dc cht d tan trong nc
nhng kh hp thu.
Cu trc este d b thy phn hoc kh ha tan, lm nh
hng n SKD ca thuc.

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 Cc yu t nh hng SKD thuc k thut bo ch

Mi dng bo ch c c im ring v thnh phn cng thc, cu trc,

k thut bo ch, cc khc bit ny c nh hng n SKD ca thuc.
SKD ca thuc c khuynh hng gim theo th t sau:

DUNG DCH NC > HN DCH NC > NANG THUC >

VIN NN > VIN BAO.

Ngoi ra trang thit b cng nh hng n cu trc l ha ca dng

thuc, do nh hng n SKD.

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 Tin b k thut trong bo ch

H thng phng thch ko di

Cc h thng hay dng thuc c kh nng phng thch hot cht mt
cch lin tc hoc gin on theo thi gian, duy tr nng hot cht
trong phm vi iu tr trong khong thi gian di, nhm gim bt s ln
dng thuc, nng cao hiu qu iu tr, gim bt tc dng khng mong
mun

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 Tin b k thut trong bo ch

H thng phng thch c kim sot

Khi hot cht c phng thch t h thng c tc phng thch hng
nh, c th tin on v chm hn bnh thng.

Cc dng thuc hay cc h thng to c tc dng tr liu v duy tr

c hiu lc iu tr trong khong thi gian di hn so vi dng quy
c c cng dc cht thng dng dng ko di c bo ch bng
cch ko di s phng thch hot cht, do 2 thut ng ny c dng
thay th nhau.

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 Tin b k thut trong bo ch

H thng tr liu a thuc n mc tiu

H thng tr liu a thuc n mc tiu l h thng c kim sot sao

cho phn ln tc nhn tr liu c phn phi mt cch chn lc n ch
tc ng, hn ch n mc ti thiu s phn phi n c quan khc gy
tc dng khng mong mun.

H thng tr liu a thuc n mc tiu c th phng thch dc cht

tc thi hoc phng thch ko di, c xem l h thng phng thch c
kim sot theo v tr tc ng.

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 Tin b k thut trong bo ch

Cng ngh nano p dng trong ngnh dc

Cc phn t thuc c ng trong cc cht mang c kch thc nano.
Cht mang v hot cht xuyn qua hng ro m v xm nhp vo t bo
mc tiu, sau hot cht c phng thch v th hin hot tnh.

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 Tin b k thut trong bo ch

Cng ngh nano p dng trong ngnh dc

u im:
- Tng ha tan ca hot cht nn tng tc dng iu tr.
- c tnh hot cht gim do liposom mng bao ph hot cht.
- Thc ch tc ng trn t bo mc tiu m khng tn hi n cc t bo
lnh.
- Gim lng thuc s dng.
- ng dng trong iu tr K bng ha tr.

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CU HI N TP TH

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Cu 1: Cho bit nn dng thuc sau theo ng no?

liu (mg) AUC (mcg/ml.h)

vin nn 100 80

dung dch ung 80 100

thuc dn 70 60

thuc tim IV 40 70
Cu 2: Cc thng s nh gi sinh kh dng ca thuc
l

a. nng ti a, thi gian bn thi, hng s tc thi

tr

b. thi gian bn thi, thi gian t nng ti a, hng

s tc hp thu.

c. hng s tc hp thu, din tch di ng cong

d. nng ti a, thi gian t nng ti a, din tch

di ng cong
Cu 3: Hai dc phm c cng loi hot cht c din
tch di ng cong bng nhau

a. cung cp cng lng dc cht cho c th nn c

xem l tng ng sinh hc

b. cung cp cng lng dc cht cho c th nhng

khng nht thit c xem l tng ng sinh hc

c. bt buc phi xem l tng ng sinh hc

d. l tng ng sinh hc khi p ng tiu chun

dc in.
Cu 4: Nng ti a trong huyt tng tng ng vi

a. thi im c tc ng dc l ti a

b. thi im c s hp thu v thi tr tng ng

c. thi im thuc bt u b chuyn ha

d. thi im c nng ti a ca dc cht trong

nc tiu.
Cu 5: Cho bit vin nn A v vin nn B c cng hot
cht v tng ng sinh hc, hy cho bit khong
AUC c th t c ca vin A

liu (mg) AUC (mcg/ml.h)

vin nn A 500 ?????

vin nn B 80 100