635
www.klinickafarmakologie.cz340804301076513320121425327329234035839843647950254457164568672477179183988990895196610061045
/26478043010732
KlinFarmakol2698804301077091109157209246273347388426473493
Farm2020;321180430107326995170224267308351367
34(4):3598804301073579104145167181
152–1573799804301073472114157196233275
/40948043010757
KLINICKÁ41718043010771114135194215268314372
FARMAKOLOGIE4564804301073383130202257304364406466525546590
A51748043010745
FARMACIE5239804301073483130203257309329372
15556558026012657110166
ORIGINÁLNÍ4694207012673138172244278352422476549582
PRÁCE5297207012661125197257315
Comparison182336501063271125160197232250282323365
of220236501063970
DOS228736501063980112
and241436501063980120
Windows254936501065876117156197256289
version285336501063768104139155196238
of310636501063970
the319036501063172104
MwPharm3309365010653112147187227263317
–3641365010646
a3702365010639
pharmacokinetic375636501063374114149204245278317353371412443477495529
software430036501063272103137199236271303
for461836501062971107
PK/PD47393650106346997132171
monitoring492536501065393135152184223259277318357
of529736501063970
digoxin53823650106385695136171189230
to34061301193182
0.25044461301194663113162209
mg)675613011977132157
taken85461301192874116163216
orally109261301195080126147168212
once1326613011950103148195
a1543613011942
day.160761301195196139152
Blood178161301194869122176231
samples34075301193887171228252303342
of70675301196391
digoxin82175301196486143199243266321
(4116675301193684
ml,1274753011980103121
EDTA1419753011956123169223
anticoa‑1666753011955111142165211265314346
gulant)340893011956111133180236267295
were659893011982132163213
obtained896893011963121153201223279330388
by1308893011965111
venipuncture1442893011955105161183240296352399434490521570
during3401033011955110140163218275
steady638103301194780129175232278
state940103301194680128159208
before11721033011964116144198229279
the1474103301194096146
morning16441033011992147179235257312368
dose.3401173011956115157212233
Serum5991173011988143177236324
digoxin9501173011996121182241288314372
concentration13491173011986144203253306365399434485520545604664
(SDC)340131301192774140201231
was5951313011982131170
determined7891313011964116148198229315337393444502
by13151313011966112
Microparticle14511313011988111158189244302351382418441488510561
Enzyme3401453011948105149200287340
Immunoassay7051453011939125211267324382431471511561608
(MEIA)13381453011944124174197259288
method165014530119102155189246303362
on3401593011953108
AxSYM4711593011962108157208286
immunology7801593011924106188242296350373427483528
analyzer13311593011949103149170215259307337
(Abbott1691159301193089145201256287322
Laboratories,340173301194593149205236283314367398420470508527
Abbott8901733011967124180236267302
Park,12151733011959105135179200
IL,143817330119297595
USA)15561733011971117175202
using17811733011962100121175231
original340187301195384106161182236282303
manufacturer’s6661873011980126180233261308354388442472520550570605
reagents1294187301192876121177226280310350
and1667187301194397153
pro‑1842187301195484137170
cedures.340201301194592148202232280318337
Therapeutic4802153011947102151180226281331384415436480
intervals982215301192982112159188237283303339
for1344215301193386116
digoxin1482215301196282137190233254307
used1811215301196097146201
in340229301192277
University4402293011976131153200250281320342374424
hospital8872293011967123161218241273321343
Ostrava12542293011980119153184232278326
are1604229301195888138
as1765229301195897
fo‑1885229301193893127
llows:34024330119214194166203220
for582243301192881110
children7142433011947100120141195224271324
0.8–2.01060243301195268118170213230279
μg/l13612433011949103139161
[6],1544243301192975101118
for1677243301192679108
adul‑18072433011948102155175206
ts340257301193272
0.5–1.2436257301196482134187232245298
μg/l7582573011951109147171
(especially,952257301194189128185238285307354377398445459
>6514342573011975126175
years)[7],16332573011959109156187227251278330360379
and340271301194699154
for516271301193487117
pregnant655271301196393141197250295349379
women10562713011980133216265318
2.0–2.51397271301195673122176220237287
μg/l17062713011949104141163
[8].1891271301193481106121
Inaccuracy340285301192277124171215270301349396445
was8082853011984132170
determined10022853011966116149198228314335391441499
using15242853011965103124179236
three1784285301194197127177228
concentration3402993011946100156203252308339371419451473528585
levels948299301193586133184206244
of1216299301196896
the13352993011945101152
commercial15112993011959113199283335366411433479502
control340313301194495147176205255276
samples.638313301193378158212233280316334
Each993313301194388131183
sample1198313301193378158212233280
was15003133011967112148
analyzed1669313301194193137157201243289343
three340327301193184113160209
times.571327301193354135184221239
Average8323273011960103150179225279328
result1182327301193179116167188218
was14223273011975120157
compared1601327301194698180234280309356411
to340341301193183
manufacturers4463413011990135189242269316361395448478526555593
declared10623413011962111157178224253301357
value14413413011953100121174223
and16863413011953107162
the1871341301193892141
bias340355301195677122159
was5213553011981127164
calculated707355301195399120165218239285315362418
(Table1148355301193484123179201250
1).142035530119577690
Acceptance15333553011966110154201256287333387432480
criteria34036930119457596127175204226271
for633369301193487117
each7723693011957102147201
analyte9953693011953107153174218253301
were13183693011980129158206
established1547369301195694126172228250270307360409465
according340383301194691134186216269290343398
to761383301193890
the873383301193993142
CLIA10373833011965109130188
Proficiency1247383301195887139166188232253302355400448
Testing1717383301195497134166187241296
Criteria340397301195989112144193224246293
[9].656397301193886112129
Precision805397301195282131179200238259315371
was11993973011985133171
determined13943973011966117149198229314336391442500
as1917397301195796
described3404113011953100136179207227280328381
in742411301191768
National8314113011958102130150201253296316
Committee11684113011952102182261280309342387435
for1624411301192172101
Clinical174641130119527190141160203247267
Laboratory340425301194695153210241290322376407457
Standards821425301196393141197254302333389427
(NCCLS)12724253011942108168223270320348
protocol16444253011971103157189243291345369
EP5-T2340439301194899147179222274
(including632439301192748103150172226283304359416
an10714393011954110
additional12044393011954111168189221243298354401423
estimate1650439301195896130151235282313362
of340453301195582
between4454533011965116148225275326381
day8494533011963110154
precision)1026453301196596145192213250271326382406
using14554533011963100121176232
human17104533011963117201248303
serum340467301193786115168250
with611467301197596127180
0.9,813467301195268115128
1.9,963467301195163109123
and11074673011949101156
3.21285467301195168118
μg/l14254673011949103139161
of1608467301195682
digoxin1712467301195778132185227248300
added3404813011945100154203258
[10].620481301192671114139154
Demographic4804953011966116199254310340387442497518564
and10664953011954108164
medical12524953011991141197218264310332
data16064953011963109139186
such1814495301194699144199
as340509301194582
age,4445093011953107156172
weight,6375093011980128148203256285303
concomitant9615093011952104157202254336356387432485515
medications,14985093011989138193213258304333354407461497514
and340523301194598153
renal515523301193683136181202
function738523301193387140185218239292345
(serum1105523301193368117146199281
creatinine1407523301195281128172202222275295348397
con‑18265233011951102156186
centration)340537301194592146176206252282303357411435
were7975373011980129158206
collected10265373011952104126146195241275323379
from1427537301193465117200
the1649537301193993142
TDM18135373011955121200
request340551301192977132184233270302
forms.663551301192779109191227245
Pharmacokinetics3405775014360123177212311365419481532559622681718743796843
PK480593301195099
calculations601593301195298118163216237281311332385439475
were10995933011979127157204
performed13255933011963113142171224254336385441
using1788593301196197117170225
two3406073011932110166
versions5316073011967118150190212269325365
of9206073011976105
MwPharm104960730119101176230285333364451
software15246073011960116145182261310341392
–19406073011973
MwPharm2140613011980155207261308339424
3.30258861301196078130180
(DOS2791613011938105175223
version,3037613011957107138177198254310328
1997)3388613011961104156203232
and3643613011957112169
MwPharm++2140753011980156210266315347434497561
1.3.5272675301197994147166219
(Windows2970753011957146171227286343419460
version,3455753011975127159200223280338357
2016).2140893011950100146191216232
The2395893011957114165
KinPop258389301196084139191244302
module2908893011993149207261283334
of326589301196492
MwPharm3380893011989163215270317347432
was21401033011974122161
used23251033011967106157215
to2563103301194599
build26861033011969125147169226
a29361033011960
one30191033011968124175
compartment32181033011959113198255304335371456507563594
model,21401173011983137193242264280
whereas24431173011980135184214262306344
previous2809117301196393141187208262316353
studies3184117301194578131187207256294
applied35001173011954109165187207256312
a21401313011945
non‑compartmental22071313011955108162192239291373427473502536617666719749794815
analysis3044131301194699144164208246265301
[11,3367131301192772110121
12].3510131301194990114130
The36611313011948103151
KinPop2140145301195072125174226281
module24431453011979132187240260309
uses2774145301195086135172
a29681453011942
two‑stage,30321453011928103155188225257302356405421
Bayesian3475145301194793136183220240284337
PK2140159301195098
analysis2260159301194698143164208245265301
procedure2583159301195584136182228284336365412
[13].3017159301192671112135151
A22801733011959
visual2361173301195374110162207228
inspection2611173301192881118172222268301322375429
of3062173301196187
each31711733011956101146199
PK33921733011958106
plasma3520173301196384129166247293
concentration2140187301194495148193239292321350395424445497550
time2712187301192747128176
curve2910187301194193122170217
in3148187301191870
MwPharmwas32401873011974145194246290319400490536572
performed21402013011955105134164217247329378434
before25962013011963112138191221268
inclusion2887201301192881126146199235255309362
of3272201301196087
these3381201301193892141178227
data36302013011962107137183
for2140215301192780111
the2273215301193994143
parametrization24392153011964111140187270320351381403444492522544598653
of3114215301196289
the3225215301193994144
PK33912153011959108
model.35222153011991145202251273291
Non‑compartmental21402293011964117170201247299380434480509543624672725754800820
parameters2982229301195297126171252301331378406444
were34482293011968116145192
also366122930119426398151
calculated2140243301194590111155208228273303349405
using2567243301195389109161216
MwPharm.28052433011977149199251296324407424
Parametrization2280258101094891121165241287317347369408453483504554605
of2904258101095683
the3006258101093686132
population31572581010958109161211233277307328378429
phar‑36052581010957108152182207
macokinetic21402721010975119159208251274324370400421462
models26212721010975125177223245280
We22802853011984135
evaluated24412853011964113163187244293327378438
two29052853011946126183
PK31142853011965118
models32582853011998156216269294334
(„di‑3618285301194177136160194
goxin“21402993011954110154177232261
/DOS24252993011945112182230
model/26782993011992147205255278316
and30182993011954109166
„digoxin_C1“3208299301193995118174229273296351405464510536
/37682993011944
WIN21403133011982105171
model/)23343133011984139196247270307339
to2697313301193386
predict2807313301195688137194216263298
the3129313301193287138
pharmacoki‑32913133011956112159190274321367421465489521
netics21403273011953103134156201241
of2404327301195178
digoxin2506327301195273128182225248301
as2831327301194380
follows:2935327301192477100121176248286304
first,326232730119244777116149168
we34533273011970119
fitted359532730119244779114161218
all214034130119456890
PK22543413011954104
parameters23823413011959107138186269320352401432471
(ka,2877341301193175295534860702629843413011917
F,3025341301195059
V,3108341301195568
Clm,3199341301196184328434860704833333413011917
fu,33743413011930340834860703134403413011917
fe,34813413011930351334860702835433413011917
fr,35843413011930361734860701736333413011917
t1/2)367434130119353707348607028487937863413011926
and394061301194598153
evaluated411661301194691137159212257288335391
their453061301192882131153182
statistics.473561301193568114144166203235257302341360
Second,511861301194493139191245300318
one5459613011950104153
by394075301195599
one,4062753011951106156173
each425975301194691137191
of447375301195179
the457575301192984133
parameters4732753011953100130177259309341389419458
was5213753011970117155
set539175301193585117
to553175301192981
Bayesian394089301195098143192231253299354
and431889301194499155
the449789301193085135
outcomes4656893011952107140184237321372411
were5091893011971120151200
statisti‑531589301193670117149171209243265297
cally3940103301194592115137183
evaluated.4147103301195097145167222268300349406426
Validation4080118101095090111132182225254274323373
of4471118101094672
the4561118101092776121
pharmacokinetic4700118101094797140169243286326374416438487532562582622
models53411181010971120171215237272
From4080131301194777133219
this4324131301194299122162
study,4511131301194883140198246261
measured47971313011994147194234290322373432
concen‑52541313011956111169217267324358
trations3940145301193164113145169225282321
of4286145301196493
individual4404145301193187144168216240297353401425
patients48531453011966115148171223279311353
assigned5230145301195696136158216272324383
to3940159301193184
digoxin4048159301195577133188232255310
were43821593011972122153202
compared4608159301194598182238286317366423
mutually,50551593011982137170225271294316362376
and54551593011946101157
to3940173301193184
calculated4048173301194795117164218241288319368425
concentrations44971733011947101156203251307338369417449471526582620
of5141173301195584
these5249173301193388139178228
in‑5501173301192479111
dividual3940187301195477124147203257304327
patients42911873011959107139161211267298338
at4653187301195081
the4758187301193691141
same4923187301194290173224
times5171187301193558141191230
with54251873011977100132188
our39402013011954109141
PK41052013011960111
models42402013011992148206257280319
in4583201301193086
MwPharm46932013011988162215270317348433
using51512013011962101123179236
their5411201301194196148170202
age,39402153011945100149166
serum4129215301193585115169250
creatinine,4402215301194272121166196218271293346396413
height,48382153011951100122176230260279
and5140215301194397152
weight.53152153011969118140194248278297
Differences3940229301196791120154206238290347395446487
of4452229301196594
<20%45712293011971123174254
between48502293011967120154234285339396
calcula‑52712293011956106129178235258307341
ted3940243301193180138
and41032433011955110167
measured42952433011991143189228283314364422
concentrations47412433011954108164212261316348380428460483539595634
were53992433011982132164214
allowed394025730119456890145219269326
[14].4290257301192875120146164
Evaluation39402835014356109164189252306342367431495
of4463283501436597
the45882835014338102161
pharmacokinetic47762835014368133187222321375429490542569632691728753806
models39402975014398163229288313357
Percentage4080313301195096124165211263292336389437
prediction4538313301195886132187206249281301353405
error4964313301195179108159187
(%PE),51723133011929100149193219232
Root54253133011953105158187
Mean39403273011977124166217
Square4178327301194194144187214260
Error445832730119426997147175
(RMSE)4653327301192270145189232258
and4926327301194596149
Bland‑Altman5095327301194565108159211240296315344424467518
plot3940341301195677130159
were41213413011979127156203
used4345341301196096145200
for4566341301193386115
prediction4702341301196392139194214258291311364417
of5141341301196086
precision5248341301196292139184204239258311365
Tab.2140359801124992147170
223283598011250
Pharmacokinetic2423360301074388133159230275312356393412458496522540578
parameters3017360301074591117159231269295332358389
of3422360301074568
digoxin3506360301074664109154190209255
Parameter217137400984585115156225267296338367
DOS3367374009855112154
WIN423837400987092147
%PE5103374009867113154
POPULATIONAL2171386009845102148201242295333355412468519559
DATA2746386009855105143190
F2171398309537
0.733983983095395392
0.6542463983095395393131
t1/221714103095256185125
(h)23134103095216584
45.1433644103095397689124159
47.6142344103095397582122156
CL217142230954681
(L/h)22704223095215788132152
6.4533794223095395493130
6.1142524223095395489120
CLm217143430954681147
(L/h/1.8523364343095215788132162199210250289
m2)264243430956627084348056232730434309521
1.433994343095394988
1.442684343095394988
V2171446309541
(L/h)22294463095215789133152
420338644630953976114
420425444630953976114
V1217145830954179
(L/kg/LBM)22674583095225789124167196233274337357
63424458309539
64292458309539
fu217147030952165
0.7533794703095395392129
0.7542474703095395392129
fe217148230952160
0.782933414823095395392129167206
0.77142284823095395392131167
fr217149430952146
0.8833774943095395394134
0.8842454943095395394134
INDIVIDUALIZED217150600982176132154203226281335385425446492534590
DATA2777506009855105143190
V2171518309541
(L)22295183095215779
354322651830953976116
(326;33605183095215996134147
572)352551830953977115136
317410751830953974107
(232;573)42325183095215999135149189227265284
-0.849765183095246680121
(-9.4;5114518309521448395134148
7.3)52795183095394686105
V1217153030954179
(L/kg/LBM)22675303095225789124167196233274337357
63286530309539
(5.8;33435303095215972113126
8.0)34875303095395493114
5.640905303095395292
(4.3;42005303095215872112125
299.5)434353030953977117129169190
-2.449685303095245973112
(-11.4;50975303095214479110120159172
8.1)52875303095395488104
fr217154230952146
0.8832025423095395394134
(0.82;33535423095226074114152166
1.05)35375423095394989127148
0.6240705423095395393131
(0.32;42185423095216074114151164
2.08)44005423095395393133153
-1.449755423095245969108
(-8.9;51005423095224485100137152
6.7)52695423095395493115
fe217155430952160
0.6332015543095395393131
(0.56;33505543095215973113152166
0.87)35335543095395394131153
0.5540735543095395393130
(0.37;42205543095216074114150161
0.87)43985543095395394131153
-0.749775543095246680119
(-5.3;5113554309521448296136148
4.1)52795543095395388104
t1/221715663095256185125
(h)23135663095216584
62.732155663095397791129
(43;33625663095215895108
135.7)348756630953973110124162184
59.440595663095397688127
(38.9;42035663095215998113151165
141.2)438656630953974108118159179
-1.849775663095245969110
(-5.2;5104566309521448295136150
3.4)52725663095395391111
Individualized21715784095175899115149166207247288304321352385426
data261257840954080104142
are27695784095406396
presented28805784095406396124158200222255296
as319057840954068
a3272578409540
median332757840956397138155195237
(interquartile35785784095213779101134157196237277300326342359393
range).398557840952361103143178198210
CL:21715884095437691
total22765884095246386125142
plasma24325884095405798125187228
clearance;26745884095335084125148186228261294308
CLm:299658840954376140153
metabolical316458840956397121160201242259275309348365
clearance;35435884095335084125148186227261294308
F:386558840953548
bioavailability;39275884095405798139173212229245286326343360376399435449
fe:43915884095205468
extrarenal44735884095346894117155178211253293310
fraction;47975884095214483116141158198240253
fr:50645884095214459
renal51385884095235697138154
fraction;53075884095204482116141157197239252
fu:21715984095206275
unbound226059840954182123164205246287
fraction;25615984095214483116141157198240253
ka:28285984095337386
absorption292859840954181108148172212236252292334
rate32775984095226184117
constant;340859840953472114141164203245267282
V:370459840954052
volume37715984095337390131194229
of401459840954061
distribution;40895984095405784107130147187228251268308350363
V1:44665984095407584
volume45645984095347390131195229
of480759840954061
distribution48835984095405783107130146187228251267308349
related52475984095235673113136169210
to547159840952463
lean21716084095165191133
body231860840954081123156
mass2488608409564104131159
Fig.340627501124771125149
2.507627501124873
Bland-Altman625628001074362107153198225274293318390435481
analysis1122628001074389134153190221238267
of1405628001074366
measured14876280010769108153183227253289335
and1838628001074389135
predicted1989628001074369106151169207234271316
SDC2321628001073892141
values247962800107357997143181212
of2707628001074366
digoxin2789628001074361106152188206252
by3057628001074379
DOS31526280010754113151
versiona,331962800107357298130147192238283299
by3635628001074379
Windows3730628001077089135180225287318
versionb,406462800107367399130147192239284298
by4379628001074379
Windows4474628001077089135180225287318
and4808628001074390135
DOSc.49596280010754113151188204
SD,5179628001073792107
Standard5302628001073761105151196241267310
Deviation340639001075696134152197223241286333