diff --git a/.github/workflows/MarkdownLinksCheck.yml b/.github/workflows/MarkdownLinksCheck.yml new file mode 100644 index 0000000..20350ca --- /dev/null +++ b/.github/workflows/MarkdownLinksCheck.yml @@ -0,0 +1,26 @@ +name: Check Markdown links + +on: + pull_request: + branches: + - review + push: + branches: + - review + +permissions: + contents: read + +jobs: + markdown-link-check: + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v2 + with: + ref: ${{ github.event.pull_request.head.sha }} + - uses: gaurav-nelson/github-action-markdown-link-check@2a60e0fe41b5361f446ccace6621a1a2a5c324cf + with: + use-quiet-mode: 'yes' + use-verbose-mode: 'yes' + config-file: '.github/workflows/mlc_config.json' + folder-path: 'report' diff --git a/.github/workflows/SpellChecker.yml b/.github/workflows/SpellChecker.yml new file mode 100644 index 0000000..fa03010 --- /dev/null +++ b/.github/workflows/SpellChecker.yml @@ -0,0 +1,17 @@ +name: Spellcheck + +on: + pull_request: + push: + +permissions: + contents: read + +jobs: + Spellcheck: + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v2 + with: + ref: ${{ github.event.pull_request.head.sha }} + - uses: rojopolis/spellcheck-github-actions@0.14.0 diff --git a/.github/workflows/XRefCheck.yml b/.github/workflows/XRefCheck.yml new file mode 100644 index 0000000..5b4ed2f --- /dev/null +++ b/.github/workflows/XRefCheck.yml @@ -0,0 +1,23 @@ +name: XRefCheck + +on: + pull_request: + branches: + - review + push: + branches: + - review + +permissions: + contents: read + +jobs: + markdown-link-check2: + runs-on: ubuntu-latest + steps: + - uses: actions/checkout@v2 + with: + ref: ${{ github.event.pull_request.head.sha }} + - uses: serokell/xrefcheck-action@959c7cecf1b316023bfd204ae88642338f6bb91c + with: + xrefcheck-args: --ignored evaluation --ignored README.md \ No newline at end of file diff --git a/.github/workflows/mlc_config.json b/.github/workflows/mlc_config.json new file mode 100644 index 0000000..00b2784 --- /dev/null +++ b/.github/workflows/mlc_config.json @@ -0,0 +1,6 @@ +{ + "retryOn429": true, + "retryCount": 5, + "fallbackRetryDelay": "30s", + "aliveStatusCodes": [200, 403] +} diff --git a/.github/workflows/wordlist.txt b/.github/workflows/wordlist.txt new file mode 100644 index 0000000..09c6952 --- /dev/null +++ b/.github/workflows/wordlist.txt @@ -0,0 +1,1281 @@ +aap +AAPS +aas +abb +Absorbability +AbsTol +Aburatani +Aciclovir +ACM +ACOS +Acta +actionToExecute +actp +actpo +AddAction +addir +addirg +addirr +addOutputInterval +addOutputs +addParameterPaths +AddPoint +addPoints +adjustbox +ADME +ae +ageMax +ageMin +ageParam +ageUnit +agg +agof +agofg +agofo +Ahonen +Ahr +ai +aintro +al +alfentanil +allAciclovirMolecules +AllOfSameType +allometric +allOutputs +allPKParameterSensitivitiesFor +allPKParametersFor +allPkParams +AllPlots +allPoints +allQuantityPaths +allUnits +anastomoses +antecubital +Anthracycline +anthropo +anthropometry +aod +ap +apkr +apkrg +apkrr +AppData +Appl +appveyor +aProperty +aps +ArrayExpress +ArterialBlood +arteriovenous +aryl +ascendingly +ASIN +ATAN +AUC +AUCinf +AUCR +AUMCs +autohidden +autoinhibition +AutoLayout +avascular +AvgUnit +AxesPredictedVsObserved +AxesResidualsOverTime +AxesResidualsVsObserved +AxesSettings +axy +Balakrishnan +Balthasar +basolateral +bended +benzoapyrene +Berezhkovskiy +Berezhkovsky +Bessems +Besten +BH +BigVial +bilayer +Bilayers +Biliary +Bioavailability +Biochem +Biochimica +Biokinetic +biologics +Biomed +Biomembrane +Biometrics +Biomolecular +Biopharm +Biopharmaceutics +Biophysica +biorelevant +Biosilico +Biotechnol +biotransformation +Bischoff +Blaauboer +Bladeren +BMC +BMI +bmiParam +BodyWeight +Bogaards +Bois +boolean +Boric +BPratio +Britz +Brodowsky +Bruelisauer +bs +Buehner +BuildingBlocks +Buist +Burghaus +Busse +BW +Bylayer +Caco +calculatePKAnalyses +callout +catabolism +catalytically +cdc +cDNA +ce +CETP +checkboxes +checkForNegativeValues +Chemother +Cheung +cholesteryl +Chosing +chronogenetics +cilostazol +Cimetidine +clarithromycin +ClassName +clearOutputIntervals +clearOutputs +clearPoints +Clewell +CLI +Clin +clogP +clrCall +Cmax +CmaxR +cmd +Coboeken +Combinatorial +combobox +comboboxes +ComparisonTimeProfile +ComparisonTimeProfilePlots +cooperativity +Costa +covariate +CRC +createIndividual +createIndividualCharacteristics +createPopulation +createPopulationCharacteristics +CreateQualificationReport +criterium +CSV +csvPKAnalysisPath +csvPopulationFile +csvResultsPath +CTRL +cumulated +CVODE +CVODES +Cyclosporin +cynomolgus +CYP +CYPs +cytochrome +cytochromes +cytosol +cytosolic +Dallmann +Danhof +Das +DashDot +dataframe +dataset +datasets +DDE +DDEs +DDI +DDIRatio +DDIRatioPlot +DDIRatioPlots +DDIRatioPlotsPredictedVsObserved +DDIRatioPlotsResidualsVsObserved +DDIRatios +De +der +Derivate +Derivates +derivedParameters +diag +Diagn +Diclofenac +digoxin +directionality +Discov +DisplayClass +displayUnit +Dispos +diss +distributedParameters +Distrubtion +dk +dlast +dm +docx +dodecyl +doIfNotCanceled +Dordas +doseParam +doseParamPath +DosePerBodyWeight +draftwatermark +Drasdo +Dressman +dropdown +dtu +Dvo +d'Yvoire +ebi +Edginton +edoc +edu +Educt +educts +EHC +Ehpgavin +EI +Einact +Eissing +Ekstrom +EMax +Enantiomeric +endhint +endosomal +Endosome +endosomes +endothelium +EndTime +entero +enterocytes +enterohepatic +entitiesList +entrez +enums +enzymesis +Enzymology +eps +epsfcn +EQ +equilibrate +erel +ersetzen +Espie +et +etoposide +EventGroup +evoZ +ewt +exe +exportPKAnalysesToCSV +exportResultsToCSV +exportSensitivityAnalysisResultsToCSV +extravascular +Fahrmeir +fancyhdr +FaSSIF +Fc +FcRn +FeSSIF +filePath +filePaths +firstorder +Fneutral +Fois +formulaString +Fphospholipid +FractionAucLastToInf +Frechen +Freijer +Frezard +fromin +fsep +ftol +fu +fvec +Fw +Galia +Garg +Garnier +gastro +Gaub +Gebhardt +GEQ +getAllContainersMatching +getAllMoleculesMatching +getAllParametersMatching +getAllXXXMatching +getContainer +getMolecule +getOSPSuiteSetting +getOutputValues +getParameter +getQuantity +getSimulationTree +getstarted +getwd +GFR +github +Gloeckner +Glomerular +glucuronide +Glucuronide +glycoprotein +GMFE +Goerlitz +GOFMergedPlot +GOFMergedPlots +GOFMergedPlotsPredictedVsObserved +GOFMergedPlotsResidualsOverTime +Göttinger +gp +Graaf +grffile +GridLines +gtol +Guentert +Gundert +Haagard +Haddad +Hafner +HandCursor +Hanke +Hanko +Haraldsson +Härter +Hartmann +Hartwig +Haruta +Hasselbalch +Hayton +HCT +heightMax +heightMin +heightUnit +Heinig +Hematocrit +Hempel +Henney +Hering +Higaki +highRes +Hindmarsh +Hissink +Hitachinaka +HLM +Hmax +Hmin +Hodjegan +Hoehn +Hohmann +Holliger +Holzhutter +Horning +hpgavin +htm +html +http +https +HumanPopulation +Hyattsville +hydrophobicity +hydroxy +hyperpolic +hyperref +IC +ico +ICRP +IgG +Ihara +ihre +img +imm +IModelCoreSimulation +impactful +importPKAnalysesFromCSV +importResultsFromCSV +importSensitivityAnalysisResultsFromCSV +inactivator +inactivators +individualCharacteristics +individualCharacterstics +IndividualId +individualIds +infMRTFractionAucLastToInf +infMRTThalfFractionAucLastToInfCLVssVd +Informa +initPKSim +InnerInvoke +InstallDir +Intellisense +intercellular +Interdiscip +interstital +intersystem +intervalName +intra +intracellular +introvideos +Inversed +InversedTime +io +ionizable +IQR +isConstant +isDistributed +ISEF +isFixedValue +isFormula +isoforms +IsPresent +isStateVariable +isTable +Itmay +Itra +Itraconazole +Jacobian +Jaeger +Jamei +Jang +Jantratid +Jongh +Joshi +json +kass +Kaumeier +Kawamura +Kawei +kcal +kcat +kcatby +Kd +kdeg +Keldenich +Kersting +Kesisoglou +KI +KIc +Kimura +kinact +kindey +kinteics +KIu +Kkinact +Kleine +klinisch +Klipid +Kneib +koff +kon +Konnen +Kprotein +Krbc +Krippendorf +Kuepfer +Kurosaki +Läbenberg +LADME +Lange +Langenbucher +lapply +lastpage +LateX +Leahy +Lehr +Lemaire +LEQ +Levenberg +Lienau +Linearization +linestyle +linestyles +lipophilic +Lipophilicity +Liposome +Liposomes +Lippert +Lippincott +livContainer +liverIntVolume +Livermore +liverVolume +livParam +llnl +LLOQ +lm +loadPopulation +loadSimulation +Lobo +logarithmically +logD +logics +logMA +LogNormal +logP +Loidl +Loizou +longtable +lowRes +Ludewig +Lustig +Mackensen +macromolecules +Madsen +Maier +ManualModel +Marquardt +MassTransferBloodPool +mathworks +maxC +MAXITER +maxt +mbdt +MBEI +mbp +MCR +md +Meister +Menten +menue +Metab +metabolization +metabolizations +metaData +Methoden +MethodsArticle +Michaelis +microarray +Microcirculation +microsomal +microsome +microsomes +microspecies +microspectrophotometry +microvascular +microvasculature +Mida +midazolam +Midorikawa +Mie +MikTex +minipig +minipigs +mL +mmHg +MoBi +Modelle +Moj +mol +MolarConcentration +MolecularWeight +moleculeInKid +moleculeOntogenies +MoleculeOntogeny +MoleculeProperties +Molweight +mongrale +monodisperse +Moxifloxacin +mRNA +MRT +MSV +mucosa +Mucosal +Multilamellar +Multiscale +multiselect +MxStep +myPopulation +MyProtein +myProteinOntogeny +Nachmann +NADPH +Naito +NCBI +nchs +nd +needspace +negativeValuesAllowed +Nelder +NEQ +Nestorov +Neuhaus +newValue +ng +NHANES +Nicholaou +Nicolaides +Niederalt +Niederberger +nifedipine +nih +NIRS +Nishimura +nlm +NLME +NMdat +nmol +Nodesize +Nonmem +novo +nP +Num +numberOfCores +numberOfIndividuals +oArmrea +ObservedData +ObservedDataRecordId +ObservedDataSets +ObserverSet +octanol +ODEInitialValues +ODEMain +ODEoptions +ODERHSFunction +ODEs +Olkkola +omeprazole +Ommen +ontogenies +OO +Opin +OrgPl +orscaled +os +OSP +OSPS +ospsuite +OSPSuiteException +ospuite +Osterholz +OutputMapping +OutputMappings +outputPath +OutputSchema +OutputSelections +oximetry +paracellular +parameterization +parameterizations +parameterName +parameterPath +parameterPaths +parentContainer +PBPK +PCR +pdf +pdflscape +PDP +Peles +Peng +perfused +pericentral +PeripheralVenousBlood +Periportal +permeabilities +permeations +pgfplots +Pgp +Pharm +Pharmacodyn +pharmacodynamic +Pharmacodynamics +Pharmacogenomics +Pharmacokinet +Pharmacokinetic +pharmacokinetics +pharmacokineticspharmacodynamics +Pharmacol +pharmacologically +pharmakokinetische +PharmSci +Phenols +phenotyping +phospholipid +phospholipids +php +physico +physicochemical +physicochemistry +Physiol +pKa +pkAnalyses +pkAnalysis +pkAnalysisLoaded +PKExcelImporter +PKj +pkml +pkmlSimulationFile +PKParameter +pKParameterFor +pkParameterName +PKParameterSensitivity +PKPD +PKRatio +PKRatioPlot +PKRatioPlots +PKRatios +pksim +placeins +PlotSettings +PlotType +pmol +PNA +png +po +Poggesi +pointwise +polydisperse +popFilePath +PopulationCharacteristics +populationResults +potentialSAParameters +potentialVariableParameterPathsFor +Poulin +Powerpoint +pre +preclinical +preconfigured +Pred +predictedVsObserved +predictivity +prefilter +pregnane +preselected +preterms +Preusser +Priori +propofol +proportionOfFemales +Proteomics +ProtocolSchemaItem +PSV +pts +pubdb +px +PXR +PxSA +Qorgan +QSP +QualificationPlan +qualificationrunner +quantitiesOrPaths +quantityPath +QuantityPKParameter +quartile +Radioecology +Radiological +Rbuildce +rClr +README +recirculation +recombinant +recombinantly +redisplayed +redisplaying +RelTol +removePoint +Remy +renally +Renkin +repo +Reppas +residualsOverTime +residualsVsObserved +restartSolver +resultOfAFunction +resultsData +resultsLoaded +resultsPath +resultsTime +resultsValues +rhCYP +RHS +RHSFormula +rifampicin +Rippe +Rizk +RMS +RND +Rodrigues +Röhring +Rostami +RRGGBB +RtmpY +RunAsync +runSensitivityAnalysis +runSimulation +Runtime +sa +Sandt +saResult +saResultLoaded +saResultPath +Sargentini +Satoh +saturable +Sawamato +sbj +SBML +scaleParameterValues +scaler +Scand +scatterers +Schlender +Schmeck +Schmitt +Schneckener +Schoenlein +Schöttner +Schwarzenbach +Schwarzmaier +scrollbars +SCum +SDZ +SectionId +sectsty +selectable +SensitivityAnalysis +sensitivityAnalysisConfig +SensitivityAnalysisResults +sep +Serban +SetA +setMoleculeInitialValues +setOutputInterval +setParameterValues +setParameterValuesByPath +setPoints +Sevestre +Shampine +sharable +SHFT +showProgress +Shumaker +Sidhu +Siegmund +sigmoid +sigmoidal +silico +Silvermann +simFilePath +SimModel +SimModelManager +simr +SimResults +simRunOptions +simTree +SimulationControl +SimulationDDI +SimulationDuration +Simulationen +SimulationParameters +SimulationPKAnalyses +SimulationResults +simulationRunner +simulationRunOptions +SimulationSettings +SINH +sinusoids +siunitx +Sj +Solodenko +SolverSettings +SpaceOrganismTemplate +spectrometric +Spendiff +Springer +SQRT +src +SRND +ssd +Stahlhofen +StandardOntogeny +StartTime +Stass +StateVariable +stateVariableParam +Steimer +stepwise +stoichiometric +stoichiometry +Stotal +Strougo +Studien +subcompartment +subcompartments +subcontainer +subcontainers +subfolder +subfolders +submenu +submodel +subpopulations +subtree +subviews +Sufentanil +Suillerot +SumMetabolites +superfamilies +supportfiles +Surg +Swiatek +Syst +TableFormula +tableParam +TableParameter +tabu +Tanaka +TANH +TargetSimulations +targetUnit +tcolorbox +tD +tDEnd +TDI +tDj +tDlast +Telle +tEnd +tEndAUC +tEndThalfAUC +Terenji +textcomp +th +Thalf +Theil +Thelen +Theophylline +Theor +Ther +thetable +threeparttablex +ths +tikz +TimeProfile +TimeUnit +Tingleff +Tlag +tlast +toBaseUnit +TOC +toDisplayUnit +tooltip +totalSensitivityThreshold +toUnit +Toxicol +Tozer +transcapillary +transcellular +transcriptional +TRANSIL +translational +TSmax +tstart +Tsutsumi +txt +typora +Tytgat +uc +UCRL +Ueffing +UGT +UI +uk +un +Uncheck +Uncompetitive +und +undissociated +Undock +ungroup +UniGene +unlink +unlinked +Unserer +unstirred +unticking +untransformed +UseDerivedValues +UseJacobian +userdefinedsnippets +USERID +Vakalopoulos +valueAt +ValuePoint +ValuePointAlreadyExistsForPointException +variabilities +variated +vasc +vascularization +VCH +Vd +VenousBlood +Vergin +Verlag +Vis +visualstudio +vitro +vitrosystem +vivo +Vmax +Voith +volumeParams +Vossen +VSCode +Vss +Watelet +WB +Weibull +weightMax +weightMin +weightUnit +Weinheim +Wendl +wikipedia +Willmann +withcellular +workstep +Wurthwein +www +xcolor +XDimension +Xenobiotica +xenografts +xls +xlsx +xml +xtol +xValues +XYZ +Yaguti +Yakugaku +Yamamoto +Yaroslavsky +Yassen +Yeo +Yoshitsugu +yout +yValues +Zasshi +Zeit +Zhu +Zischka +zonated +zonation +Zwitterions +OSPSuite +csv +mucosal +rhsFormula +rhs +simulationResults +outputSchema +endTime +outputSchema +startTime +populationCharacteristics +pkParameter +PKAnalyses +outputSelections +SAResult +pharmacokinetic +multiscale +Anwendung +nhanes +ncbi +unigene +de +itraconazole +Emax +pharmacodynamics +bioavailability +biliary +glomerular +lipophilicity +endosome +Ki +NonMem +userid +jacobian +uncheck +Ctrl +QualificationRunner +educt +biometrics +tDi +dDi +PKSim +hematocrit +pka +periportal +uncompetitive +basolat +bbb +brn +intracellularly +IVIVE +localizations +Localizations +luminal +vasculature +vmax +pls +vasend +bc +endo +PortalVein +BloodCells +DV +DVID +DVNAME +DVUNIT +nmdat +NaN +WIP +vas +closable +basolatateral +runAsync +simulationRunArgs +runtime +LLOQs +Lloq +closeable +Anwendungen +Claassen +CMax +CPT +doi +Ince +Jia +Jonsson +Mavroudis +PBTK +Pharmacometrics +PLoS +Preuss +psp +Sjögren +Teutonico +toxicokinetics +Validator +Workgroup +Curr +Des +EFPIA +jcph +JF +Tarning +TG +preselect +Arterialized +GLP +ables +igures +istings +tlf +reportingengine +parameteridentification +addfd +Agúndez +Analg +Andresen +anes +Anesth +anthropometric +Asada +Bocxlaer +Camu +cfa +cfc +Cockshott +codebases +Coppens +covariates +CY +diphospho +Doufas +Drugbank +drugbank +EJ +Enzymol +EP +Epub +Funae +Gambus +Gepts +glucuronidation +glucuronosyltransferase +Glucuronosyltransferases +Goodale +Goto +GPLv +Hamaoka +Hase +Hiraoka +Hiroi +Horiuchi +hydroxylation +Imaoka +incubations +Ishizaki +Isoform +Jaehde +Jahdari +JFP +JX +Krauss +Martín +Martínez +Mazoit +Minto +MJ +mM +MMRF +Mortier +Nakamura +Neve +Oda +opentci +OSPy +overprediction +Restrepo +Samii +Schnider +Shafer +SL +Struys +Takizawa +TW +UDP +Uridine +vx +WS +Youngs +pbpk diff --git a/.spellcheck.yml b/.spellcheck.yml new file mode 100644 index 0000000..462c4a8 --- /dev/null +++ b/.spellcheck.yml @@ -0,0 +1,18 @@ +matrix: +- name: Markdown + aspell: + lang: en + dictionary: + wordlists: + - .github/workflows/wordlist.txt + encoding: utf-8 + pipeline: + - pyspelling.filters.markdown: + - pyspelling.filters.html: + comments: false + ignores: + - code + - pre + sources: + - '**/*.md' + default_encoding: utf-8 diff --git a/Evaluation/Input/Content/References.md b/Evaluation/Input/Content/References.md index 45642ae..04a6c07 100644 --- a/Evaluation/Input/Content/References.md +++ b/Evaluation/Input/Content/References.md @@ -12,13 +12,13 @@ **Ezuruike 2018** Ezuruike U, Humphries H, Dickins M, Neuhoff S, Gardner I, Rowland Yeo K. Risk–Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach. *Clin Pharmacol Ther*. 2018;104(6):1229-1239 -**FDA. QUARTETTE ** FDA. QUARTETTE (levonorgestrel/ethinyl estradiol and ethinyl estradiol) tablets, for oral use. Website: accessdata.fda.gov/drugsatfda_docs/label/2013/204061s000lbl.pdf.2013. +**FDA. QUARTETTE** FDA. QUARTETTE (levonorgestrel/ethinyl estradiol and ethinyl estradiol) tablets, for oral use. Website: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204061s000lbl.pdf **Goebelsmann 1986** Goebelsmann U, Hoffman D, Chiang S, Woutersz T. The relative bioavailability of levonorgestrel and ethinyl estradiol administered as a low-dose combination oral contraceptive. *Contraception*. 1986;34(4):341-351. **Granfors 2005** Granfors MT, Backman JT, Laitila J, Neuvonen PJ. Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2. *Clin Pharmacol Ther*. 2005;78(4):400-411. -**Karjalainen 2008** Karjalainen, M. (Thesis, 2008). Inhibition of CYP1A2-mediated drug metabolism in vitro and in humans: With special emphasis on rofecoxib and other NSAIDs. Website: helda.helsinki.fi/bitstream/handle/10138/23039/inhibiti.pdf?sequence=1&origin=publication_detail +**Karjalainen 2008** Karjalainen, M. (Thesis, 2008). Inhibition of CYP1A2-mediated drug metabolism in vitro and in humans: With special emphasis on rofecoxib and other NSAIDs. Website: https://helda.helsinki.fi/bitstream/handle/10138/23039/inhibiti.pdf?sequence=1&origin=publication_detail **Kothare 2012** Kothare PA, Seger ME, Northrup J, Mace K, Mitchell MI, Linnebjerg H. Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial. *BMC Clin Pharmacol*. 2012;12:8. @@ -34,9 +34,9 @@ **Sidhu 2006** Sidhu J, Job S, Singh S, Philipson R. The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. *Br J Clin Pharmacol*. 2006;61(2):191-199. -**SmPC Namuscla ** SmPC Namuscla 167 mg hard capsules, 2019, website medicines.org.uk/emc/product/9838/smpc +**SmPC Namuscla** SmPC Namuscla 167 mg hard capsules, 2019, website https://www.medicines.org.uk/emc/product/9838/smpc -**Stanczyk 1983** Stanczyk FZ, Mroszczak EJ, Ling T, et al. Plasma levels and pharmacokinetics of norethindrone and ethinylestradiol administered in solution and as tablets to women. *Contraception*. 1983;28(3):241-251.. +**Stanczyk 1983** Stanczyk FZ, Mroszczak EJ, Ling T, et al. Plasma levels and pharmacokinetics of norethindrone and ethinylestradiol administered in solution and as tablets to women. *Contraception*. 1983;28(3):241-251. **Stanczyk 2013** Stanczyk FZ, Archer DF, Bhavnani BR. Ethinyl estradiol and 17beta-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. *Contraception*. 2013;87(6):706-727. @@ -52,6 +52,6 @@ **Willmann 2007** Willmann S, Höhn K, Edginton A, Sevestre M, Solodenko J, Weiss W, Lippert J, Schmitt W. Development of a physiology-based whole-body population model for assessing the influence of individual variability on the pharmacokinetics of drugs. *J Pharmacokinet Pharmacodyn* 2007, 34(3): 401-431. -**Zanaflex prescribing information** Zanaflex prescribing information. Website: accessdata.fda.gov/drugsatfda_docs/label/2006/020397s021,021447s002lbl.pdf, 2006, Acorda Therapeutics Inc +**Zanaflex prescribing information** Zanaflex prescribing information. Website: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020397s021,021447s002lbl.pdf , 2006, Acorda Therapeutics Inc **Zhang 2017** Zhang C, Li H, Xiong X, et al. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch. *Drug Des Devel Ther*. 2017;11:725-731. \ No newline at end of file diff --git a/Evaluation/Input/Content/Section1_Introduction.md b/Evaluation/Input/Content/Section1_Introduction.md index efe171d..51c1f5c 100644 --- a/Evaluation/Input/Content/Section1_Introduction.md +++ b/Evaluation/Input/Content/Section1_Introduction.md @@ -6,10 +6,10 @@ Ethinylestradiol is an estrogen medication which is used widely as a birth contr **Distribution**: ethinylestradiol is rapidly distributed throughout most body tissues with the largest concentration found in adipose tissue. It distributes into breast milk, with low concentrations. More than 80% of ethinylestradiol in serum is conjugated as sulphate and almost all the conjugated form is bound to albumin. -**Metabolism**: ethinylestradiol is metabolised in the liver. Hydroxylation appears to be the main metabolic pathway. 60% of a dose is excreted in the urine and 40% in the faeces. +**Metabolism**: ethinylestradiol is metabolized in the liver. Hydroxylation appears to be the main metabolic pathway. 60% of a dose is excreted in the urine and 40% in the faeces. **Excretion**: About 30% is excreted in the urine and bile as the glucuronide or sulphate conjugate. The rate of metabolism of ethinylestradiol is affected by several factors, including enzyme-inducing agents, antibiotics, and cigarette smoking. The elimination half-life of ethinylestradiol ranges from 5 to 16 hours. -After i.v administration, ethinylestradiol displays approximately linear dose relationship in the dose range 30-100 µg. A wide variability is present in the terminal part of the dose-normalized concentrations. +After i.v. administration, ethinylestradiol displays approximately linear dose relationship in the dose range 30-100 µg. A wide variability is present in the terminal part of the dose-normalized concentrations. After p.o. single dose, ethinylestradiol shows linear dose relationship in the dose range 30-3000 µg. Secondary peaks can be observed in individual data, compatible with enterohepatic re-circulation. However, mean data do not display such feature as a result of such peak being averaged out. Therefore, enterohepatic re-circulation was not taken into account in the model. diff --git a/Evaluation/Input/Content/Section2.2_Data.md b/Evaluation/Input/Content/Section2.2_Data.md index a265674..97fea12 100644 --- a/Evaluation/Input/Content/Section2.2_Data.md +++ b/Evaluation/Input/Content/Section2.2_Data.md @@ -1,6 +1,6 @@ ### 2.2.1 In vitro and physico-chemical data -A literature search was performed to collect available information on physico-chemical properties of ethinylestradiol ([Table 1](#Table 1)). +A literature search was performed to collect available information on physico-chemical properties of ethinylestradiol, see [Table 1](#table-1). | **Parameter** | **Unit** | **Value** | Source | **Description** | | :------------------------------ | ----------------- | ---------------- | --------------------------------- | ---------------------------------------------- | @@ -16,14 +16,14 @@ A literature search was performed to collect available information on physico-ch | Km UGT1A1+ | µmol/l | 19.22 | [Ezuruike 2018](#5-references) | UGT1A1 saturation constant | | Vmax UGT1A1+ | pmol/min/mg prot. | 408.5 | [Ezuruike 2018](#5-references) | Maximal metabolization rate by UGT1A1 | | Renal Elimination+ | l/h | 2.079 | [Stanczyk 2013](#5-references) | Renal clearance | -| Clint HLM+ | µL/min/mg prot. | 118.83 | [Ezuruike 2018](#5-references) | Inttrinsic clearance in Human Liver Microsomes | +| Clint HLM+ | µL/min/mg prot. | 118.83 | [Ezuruike 2018](#5-references) | Intrinsic clearance in Human Liver Microsomes | | Ki CYP1A2 | µmol/l | 10.6 | [Karjalainen 2008](#5-references) | CYP1A2 inhibition constant | -**Table 1:** Physico-chemical and *in-vitro* metabolization properties of ethinylestradiol extracted from literature. *+: Value used in final model* +**Table 1:** Physico-chemical and *in-vitro* metabolization properties of ethinylestradiol extracted from literature. *+: Value used in final model* ### 2.2.2 Clinical data -A literature search was performed to collect available clinical data on ethinylestradiol ([Table 2](#Table 2)). +A literature search was performed to collect available clinical data on ethinylestradiol, see [Table 2](#table-2). | **Source** | Route | **Dose [mg]/** **Schedule \*** | **Pop.** | **Sex** | **N** | **Form.** | | -------------------- | ------------------------------- | ------------ | ------- | --------------------------------- | --------------------------------- | --------------------------------- | @@ -44,4 +44,4 @@ A literature search was performed to collect available clinical data on ethinyle | [Kothare 2012](#5-references)+ | p.o. | 0.03/0.03 q.d. | HV | F | 20 | tablet | | [Timmer 2000](#5-references)+ | p.o. | 0.03 | HV | F | - | tablet | -**Table 2:** Literature sources of clinical concentration data of ethinylestradiol used for model development and validation. *\*: single dose unless otherwise specified;+: Data used for final parameter identification* \ No newline at end of file +**Table 2:** Literature sources of clinical concentration data of ethinylestradiol used for model development and validation. *\*: single dose unless otherwise specified;+: Data used for final parameter identification* \ No newline at end of file diff --git a/Evaluation/Input/Content/Section2.3_Model_Parameters_and_Assumptions.md b/Evaluation/Input/Content/Section2.3_Model_Parameters_and_Assumptions.md index 3d9da36..c14a83a 100644 --- a/Evaluation/Input/Content/Section2.3_Model_Parameters_and_Assumptions.md +++ b/Evaluation/Input/Content/Section2.3_Model_Parameters_and_Assumptions.md @@ -23,7 +23,7 @@ Renal plasma clearance is modeled with `Plasma clearance` set to 2.079 l/h repor ### 2.3.4 Enzyme Inhibition -Simulations of co-administration of ethinylestradiol with tizanidine (see [CYP1A2 DDI Qualification report](link)) indicate that the reported competitive inhibition of CYP1A2 by ethinylestradiol ([Karjalainen 2008](#5-references)) is not sufficient to describe the increased concentrations of tizanidine after multiple days administration. Therefore, it was decided to fit a time-dependent inhibition (TDI) function to the CYP1A2 enzyme system. The parameters `Kinact` and `K_kinact_half` were estimated by fitting the model to concentration-time profiles of tizanidine ([Granfors 2005](#5-references)). +Simulations of co-administration of ethinylestradiol with tizanidine (see [CYP1A2 DDI Qualification report](https://github.com/Open-Systems-Pharmacology/OSP-Qualification-Reports/releases)) indicate that the reported competitive inhibition of CYP1A2 by ethinylestradiol ([Karjalainen 2008](#5-references)) is not sufficient to describe the increased concentrations of tizanidine after multiple days administration. Therefore, it was decided to fit a time-dependent inhibition (TDI) function to the CYP1A2 enzyme system. The parameters `Kinact` and `K_kinact_half` were estimated by fitting the model to concentration-time profiles of tizanidine ([Granfors 2005](#5-references)). ### 2.3.5 Automated Parameter Identification diff --git a/Evaluation/Input/Content/glossary.md b/Evaluation/Input/Content/glossary.md index 6b02d33..0428812 100644 --- a/Evaluation/Input/Content/glossary.md +++ b/Evaluation/Input/Content/glossary.md @@ -44,7 +44,7 @@ | q.d. | Once daily (quaque diem) | | SD | Single Dose | | SE | Standard error | -| s.d.SPC | Single doseSummary of Product Characteristics | +| s.d.SPC | Single dose Summary of Product Characteristics | | SD | Standard deviation | | TDI | Time dependent inhibition | | t.i.d | Three times a day (ter in die) | diff --git a/Evaluation/Workflow.m b/Evaluation/Workflow.m index f256db1..3011b1c 100644 --- a/Evaluation/Workflow.m +++ b/Evaluation/Workflow.m @@ -7,9 +7,9 @@ % -------------------------------------------------------------- % replace qualificationRunnerFolder and markdownJoinerFolder with your paths -qualificationRunnerFolder = 'c:\Program Files\Open Systems Pharmacology\QualificationRunner 9.0'; -markdownJoinerFolder = 'c:\Program Files\Open Systems Pharmacology\markdown-joiner'; -PKSimPortableFolder = 'd:\Work\PK-Sim\'; +qualificationRunnerFolder = 'c:\Program Files\Open Systems Pharmacology\QualificationRunner 10'; +markdownJoinerFolder = 'c:\Program Files\Open Systems Pharmacology\markdown-joiner\'; +PKSimPortableFolder = 'd:\Work\OSPS\Repos\PK-Sim10.0\'; % -------------------------------------------------------------- % replace basisDir and qualificationPlanName with your paths