Download - Pharmacokinetics (II) 藥物動力學
![Page 1: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/1.jpg)
Pharmacokinetics (II)Pharmacokinetics (II)藥物動力學藥物動力學
鮑力恒鮑力恒
國防醫學院藥學系國防醫學院藥學系
![Page 2: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/2.jpg)
![Page 3: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/3.jpg)
![Page 4: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/4.jpg)
![Page 5: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/5.jpg)
![Page 6: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/6.jpg)
階段階段 藥物探索藥物探索 藥物開發藥物開發 臨床前試臨床前試驗驗
PhaseⅠPhaseⅠ PhaseⅡPhaseⅡ PhaseⅢPhaseⅢ PhaseⅣPhaseⅣ
時程時程 XX 年年 1~31~3 年年 1~21~2 年年 0.5~10.5~1 年年 1~21~2 年年 2~32~3 年年 長期長期
目的目的 先導化合先導化合物探索物探索 , , 藥物設計藥物設計 ,, 藥物製藥物製備備 , , 活性活性篩選篩選
藥物最適藥物最適化化 , , 藥物藥物製劑開發製劑開發 ,, 藥劑開藥劑開發發
生物安全生物安全性及活性性及活性試驗試驗
安全性及安全性及劑量劑量
有效性及有效性及不良反應不良反應
確認有效確認有效性性 , , 長期長期使用之不使用之不良反應監良反應監測測
安全性安全性
取樣人數取樣人數 ---- ---- 實驗室及實驗室及動物試驗動物試驗
20~10020~100名健康志名健康志願者願者
100~400100~400名志願病名志願病患患
1000~3001000~30000 名志願名志願病患病患
長期觀察長期觀察服用者服用者
成功率成功率(%)(%)
-0.00-0.00 -0.1-0.1 2.52.5 7070 3333 2525
經費經費 (( 千千萬美元萬美元 ))
0.5~20.5~2 1~21~2 2.5~32.5~3 3~3.53~3.5 8~98~9 2020
![Page 7: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/7.jpg)
![Page 8: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/8.jpg)
Early and Late Phase StudiesⅠEarly and Late Phase StudiesⅠEarly Late
First administration First repeat dose Pilot pharmacokinetics/ p
harmacodynamics
Definitive pharmacokinetics/pharmacodynamicsBioavailabilityNew formulationsInteraction studies Drug/food Drug/drugMetabolic disposition Hepatic impairment Renal impairment Pharmacokinetics in the young and elderly
![Page 9: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/9.jpg)
![Page 10: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/10.jpg)
Single-dose pharmacokineticsRepeated-dose pharmacokineticsAbsolute systemic bioavailabilityFood effects Dose proportionality Mass balanceMetabolismTherapeutic monitoring during efficacy and safety studies
Phase 2 Clinical Studies Involving Pharmacokinetics
![Page 11: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/11.jpg)
Phase 3 Clinical Studies Involving Pharmacokinetics
Therapeutic drug-level monitoring of safety and efficacy trials Special patient populationsRenal failureHepatic failureElderly versus young Drug interactionsBioavailability/bioequivalence of market-image versus clinical trial formulations
![Page 12: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/12.jpg)
![Page 13: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/13.jpg)
生體可用率與生體相等性生體可用率與生體相等性
學名藥與原開發廠學名藥與原開發廠國產藥品與國外進口藥品國產藥品與國外進口藥品
![Page 14: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/14.jpg)
藥品含量 藥品主成份含量均一度 藥品之安定性 藥品之溶離試驗等 符合藥典之規定
體外品管之指標
![Page 15: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/15.jpg)
A 廠 = B 廠 A廠藥效 = B 廠藥效
?
![Page 16: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/16.jpg)
![Page 17: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/17.jpg)
體內品管之指標 – 生體可用率
藥品有效成份由製劑中吸收進入全身血液循環或作用部位之量與速率之指標。
![Page 18: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/18.jpg)
血漿
中藥
物濃
度
體內品管之指標 – 生體可用率 (BA)
時間
最高濃度:吸收之速率
曲線下之面積:吸收進入體內之量
![Page 19: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/19.jpg)
![Page 20: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/20.jpg)
以相同條件給予同一組人:–隨機交叉試驗方式,以減少個體間之差異
生體相等性 (BE)
試驗期一試驗期一 試驗期二試驗期二
第一組試驗者第一組試驗者 A A 藥藥 B B 藥藥
第二組試驗者第二組試驗者 B B 藥藥
A A 藥藥
![Page 21: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/21.jpg)
生體相等性 (BE)
血漿
中藥
物濃
度
時間
- 原製造廠
- 非原製造廠
![Page 22: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/22.jpg)
生體相等性 (BE) 之判斷血
漿中
藥物濃
度
時間
血漿中
藥物濃
度
時間血
漿中藥
物濃
度
時間
![Page 23: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/23.jpg)
![Page 24: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/24.jpg)
新劑型的研發
![Page 25: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/25.jpg)
控釋劑型之設計控釋劑型之設計
藥物自控釋劑型中釋出之量:藥物自控釋劑型中釋出之量:藥物之藥動性質藥物之藥動性質治療濃度治療濃度用藥頻率用藥頻率
![Page 26: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/26.jpg)
DDtottot = D = Dii + D + Dmm
DDi i :: 初始劑量初始劑量DDm m : : 維持劑量維持劑量 - - 以以 zero-order(kzero-order(k00)) 釋出維持釋出維持 ttdd 時間時間
DDtottot = D = Dii + k + k0 0 ttdd
DDtottot = D = Dii - k - k00ttpp+ k+ k0 0 ttdd
ttd d : : 到達最高濃度所需之時間到達最高濃度所需之時間
控釋劑型之設計 – 劑量之計算
![Page 27: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/27.jpg)
![Page 28: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/28.jpg)
控釋劑型之設計 – 釋出之速控釋劑型之設計 – 釋出之速率率
到達穩定狀態到達穩定狀態Rate in = Rate outRate in = Rate out
藥物自體內清除之速率 :藥物自體內清除之速率 : ClClTT (ml/mi (ml/mi
n)n)ClClTT (ml/min) x C (ml/min) x Cpp (μg/ml) = μg/min (μg/ml) = μg/min
KK00 = Cl = ClTT C Cpp
![Page 29: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/29.jpg)
Dtot = ClT Cp τ
![Page 30: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/30.jpg)
Transdermal dosage formTransdermal dosage form穿皮製劑穿皮製劑
如何判斷是否該出方之實用性?
穿皮速率是否足夠?
![Page 31: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/31.jpg)
體外穿皮試驗體外穿皮試驗流量 流量 (Flux)(Flux) :單位時間內穿擴單位面:單位時間內穿擴單位面積之藥量積之藥量
體外實驗之結果體外實驗之結果
PCSdt
dMJ
此可視為單位面積藥物之給藥速率
![Page 32: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/32.jpg)
治療濃度:治療濃度: CpCp藥物之清除率:藥物之清除率: ClCl
藥物自體內之清除速率:藥物自體內之清除速率: RR R = Cl*CpR = Cl*Cp
製劑面積大小 製劑面積大小 = Cl*Cp / J= Cl*Cp / J可知是否要製成背心穿在身上才會有效可知是否要製成背心穿在身上才會有效
![Page 33: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/33.jpg)
![Page 34: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/34.jpg)
臨床藥物治療監測臨床藥物治療監測Therapeutic Drug MonitoringTherapeutic Drug Monitoring
TDM TDM - Applied Pharmacokinetics- Applied Pharmacokinetics
![Page 35: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/35.jpg)
![Page 36: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/36.jpg)
![Page 37: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/37.jpg)
![Page 38: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/38.jpg)
Steady-stateSteady-state
Rate in = F . Dose / t
Unit : mg/hr
Rate out = Css . CL
Unit : mg/L . L/hr = mg/hr
![Page 39: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/39.jpg)
例題:例題:•一男性 Asthma 病患: 40 歲,體重: 70 Kg ,如給予 Aminophylline IV infusion( 點滴 ) ,則其 Loading dose ( 初始劑量 )是多少 ?
•兩天以後,病患出院,改以口服之劑型,病患之服藥劑量應是多少?要多久服用一次?
![Page 40: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/40.jpg)
![Page 41: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/41.jpg)
Population PharmacokineticsPopulation Pharmacokinetics
![Page 42: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/42.jpg)
![Page 43: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/43.jpg)
Source of variabilitySource of variability
Drug is distributed in the bodyModern Drug Delivery
The drug.
Drug acts on the bodyPharmacodynamicsEfficacy and Toxicity
Clinical endpoint
Body acts on the drug, ADME, Pharmacokinetics
![Page 44: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/44.jpg)
Clinical data are sparse and observational. Population mixed- effect Clinical data are sparse and observational. Population mixed- effect modeling method is a fundamental tool for characterizing the multi –modeling method is a fundamental tool for characterizing the multi –
dimensional relationships with sparse datadimensional relationships with sparse data
Time (h)
Dru
g C
on
cen
tra
tion
0 2 4 6 8 10 12
0.0
0.0
20
.04
0.0
6
Extensive PK
Time (h)
Dru
g C
on
cen
tra
tion
0 1 2 3 4 5 6
0.0
0.0
50
.10
0.1
50
.20
Sparse PK
Time (h)
Dru
g C
once
ntr
atio
n
0 1 2 3 4 5 6
0.0
0.0
50
.10
0.1
50
.20
Mixed Effects Modeling
ExposureExposure
Exposure
Effe
ct(%
)
0 2 4 6 8
02
04
06
08
01
00
Efficacy
Exposure
pro
ba
lity(
DLT
)
0 2 4 6 8 10 120
.00
.20
.40
.60
.81
.0
Safety
Choice of Dosage Regimen
![Page 45: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/45.jpg)
PopulationPopulation approachapproach To utilize sparse data in data analysisTo utilize sparse data in data analysis To handle mixed data setsTo handle mixed data sets To screen covariates that impact drug’s kinetic To screen covariates that impact drug’s kinetic
and dynamic propertiesand dynamic properties To model random inter-subject, intra-subject, To model random inter-subject, intra-subject,
as well as inter-occasion variabilitiesas well as inter-occasion variabilities To estimate individual kinetic and/or dynamic To estimate individual kinetic and/or dynamic
parameters via post hocparameters via post hoc To simultaneously model kinetic, dynamic, and To simultaneously model kinetic, dynamic, and
safety datasafety data
![Page 46: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/46.jpg)
SoftwareSoftware Software used for modeling: Software used for modeling:
S-PLUSS-PLUS WinNonMix WinNonMix PpharmPpharm SAAM II Pop SAAM II Pop NONMEMNONMEM OtherOther
Software used for model automation: Software used for model automation: ExposeExpose WinBugs WinBugs WAMWAM OtherOther
Software validationSoftware validation Software modificationSoftware modification Custom softwareCustom software
![Page 47: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/47.jpg)
Examples: Pediatric PKExamples: Pediatric PK Number of subject are limited Number of subject are limited Measurements are sparse, unbalanced, and very limited.Measurements are sparse, unbalanced, and very limited. PK characteristics may differ from those of Adults or unknPK characteristics may differ from those of Adults or unkn
ownown CL may be a function of Age, or BSACL may be a function of Age, or BSA Vd may be a function of WTVd may be a function of WT Poor protocol compliancePoor protocol compliance Product development time lineProduct development time line Cost in increasing N vs. increasing nCost in increasing N vs. increasing n Competitors marketCompetitors market Age or WT data treated as groups vs. as continuous variaAge or WT data treated as groups vs. as continuous varia
bles.bles.
![Page 48: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/48.jpg)
Sampling time optionsSampling time options
0
1
2
3
4
5
6
0 5 10 15 20 25 30
Time (hours)
Co
nc.
(ug
/ml)
0
1
2
3
4
5
6
0 5 10 15 20 25 30
Time (hours)
Co
nc.
(ug
/ml)
0
1
2
3
4
5
6
0 5 10 15 20 25 30
Time (hours)
Co
nc.
(ug
/ml)
0
1
2
3
4
5
6
0 5 10 15 20 25 30
Time (hours)
Co
nc.
(ug
/ml)
![Page 49: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/49.jpg)
Sampling OptionsSampling Options
0
2
4
6
8
10
12
14
0 10 20 30 40 50 60 70 80 90 100
Time (hours)
Co
nc.
(u
g/m
l)
0
2
4
6
8
10
12
14
0 10 20 30 40 50 60 70 80 90 100
Time (hours)
Co
nc.
(u
g/m
l)
0
2
4
6
8
10
12
14
0 10 20 30 40 50 60 70 80 90 100
Time (hours)
Co
nc.
(u
g/m
l)
0
2
4
6
8
10
12
14
0 10 20 30 40 50 60 70 80 90 100
Time (hours)
Co
nc.
(u
g/m
l)
![Page 50: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/50.jpg)
Pediatric PK studyPediatric PK study
TIME
DV
0 5 10 15 20
05
10
15
Conc vs. Time, STS method
TIME
DV
0 5 10 15 20
02
46
810
Conc vs. Time, POP method
![Page 51: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/51.jpg)
Results - Ped. Study (cont.)Results - Ped. Study (cont.)0
24
68
10
12
1 2 3 4
Group
CL
PPK method
02
46
81
01
2
1 2 3 4
Group
CL
s
STS method
![Page 52: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/52.jpg)
Results - Ped. Study (cont.)Results - Ped. Study (cont.)0
20
40
60
80
1 2 3 4
Group
V
PPK method
02
04
06
08
0
1 2 3 4
Group
Vs
STS method
![Page 53: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/53.jpg)
Results - Ped. Study (cont.)Results - Ped. Study (cont.)0
12
34
5
1 2 3 4
Group
KA
PPK method
01
23
45
1 2 3 4
Group
KA
s
STS method
![Page 54: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/54.jpg)
Results - Ped. Study (cont.)Results - Ped. Study (cont.)
CL
CL
s
2 4 6 8 10
24
68
10
12
14
Regression CLpop vs CL
![Page 55: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/55.jpg)
Results - Ped. Study (cont.)Results - Ped. Study (cont.)
V
Vs
0 20 40 60
02
04
06
08
0
Regression Vpop vs V
![Page 56: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/56.jpg)
![Page 57: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/57.jpg)
PK-PD modelingPK-PD modeling
![Page 58: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/58.jpg)
![Page 59: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/59.jpg)
![Page 60: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/60.jpg)
![Page 61: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/61.jpg)
CARDIOVASCULAR EFFECT AND SIMULTANEOUS PHARMACOKINETIC AND
PHARMACODYNAMIC MODELING OF PIMOBENDAN IN HEALTHY NORMAL SUBJECTS
KAI-MIN CHU, OLIVER YOA-PU HU, AND SHYH-MING SHIEHPharmaceutical Research Institute, National Defense Medical Center (O.Y.-P.H.)
and Division of Cardiology, Department of Medicine,Tri-Service General Hospital, National Defense Medical Center (K.-M.C., S.-M.S.),
Taipei, Taiwan, Republic of China(Received September 11, 1998; accepted February 10, 1999)
This paper is available online at http://www.dmd.org
![Page 62: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/62.jpg)
Pimobendan is an inotropic agent with vasodilator properties.
![Page 63: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/63.jpg)
![Page 64: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/64.jpg)
![Page 65: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/65.jpg)
![Page 66: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/66.jpg)
![Page 67: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/67.jpg)
There was a delay between the peaking time of plasma pimo concentration and the Emax (changes in LVESD)
![Page 68: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/68.jpg)
![Page 69: Pharmacokinetics (II) 藥物動力學](https://reader033.vdocuments.site/reader033/viewer/2022061415/56814622550346895db32b7c/html5/thumbnails/69.jpg)
Good Jobs