2025
Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study
Dahl K, Toubro S, Dey S, Duque do Vale R, Flint A, Gasiorek A, Heydorn A, Jastreboff A, Key C, Petersen S, Vegge A, Adelborg K. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. The Lancet 2025 PMID: 40550231, DOI: 10.1016/s0140-6736(25)01185-7.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAmylin receptor agonistAdverse eventsGLP-1Receptor agonistsTreatment durationPlasma concentration-time curvePhase 1b/2a studyConcentration-time curveMaximum plasma concentrationEarly-phase studiesClinical Research CentreRandomised controlled studyProportion of discontinuationBaseline bodyweightPart BTolerability profileMaintenance dosePlacebo-ControlledGastrointestinal eventsPrimary endpointSecondary endpointsFull analysisWeight loss propertiesPlasma concentrationsDevelopment of Rifampicin Eye Drops for the Treatment of Exudative Age-Related Macular Degeneration
Vailoces V, Tolentino A, Arevalo J, Adelman R, Bhisitkul R, V. D, Nguyen Q, Tolentino M, Tanito M, Serizawa H. Development of Rifampicin Eye Drops for the Treatment of Exudative Age-Related Macular Degeneration. Pharmaceuticals 2025, 18: 655. PMID: 40430474, PMCID: PMC12115180, DOI: 10.3390/ph18050655.Peer-Reviewed Original ResearchExudative age-related macular degenerationAge-related macular degenerationOxygen-induced retinopathyChoroidal neovascularizationMacular degenerationTopical applicationEffective doseTreatment of exudative age-related macular degenerationMouse laser-induced choroidal neovascularizationMouse laser-induced CNV modelTreatment of exudative macular degenerationInhibit neovascularizationRat oxygen-induced retinopathyLaser-induced choroidal neovascularizationLaser-induced CNV modelExudative macular degenerationDose-escalation studyPrevent vision lossDoses of rifampicinInhibition of neovascularizationConcentration-time curveAdministration of rifampicinAnti-angiogenesis effectDose-dependent mannerAnti-angiogenic properties
2024
Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review
Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan A. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review. Journal Of Oncology Pharmacy Practice 2024, 30: 721-736. PMID: 38509812, PMCID: PMC11118786, DOI: 10.1177/10781552241238979.Peer-Reviewed Original ResearchOral hypomethylating agentsAcute myeloid leukemiaHypomethylating agentsPK-PD profilesPharmacokinetic (PK)-pharmacodynamicMyeloid leukemiaTreatment selectionPK-PDConcentration-time curveIntravenous (IVImprove treatment outcomesCC-486IV decitabineOral azacitidineMaintenance therapySubcutaneous azacitidineNo significant differenceImprove quality of lifeAzacitidineClinical trialsClinical activityTreatment outcomesDisease settingsDecitabineDisease outcome
2023
Pharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects
Zhang Q, Sun C, Wu J, Wu J, Zhang X, Liu Y, Dou C, Qin H, Zhang Q, Zhou R, Hu W. Pharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects. Expert Opinion On Biological Therapy 2023, 23: 727-735. PMID: 36880118, DOI: 10.1080/14712598.2023.2189009.Peer-Reviewed Original ResearchConceptsHealthy Chinese male subjectsChinese male subjectsGeometric mean ratiosMale subjectsImmunogenicity profilePK parametersGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsChinese Clinical Trial RegistryCardiovascular adverse eventsParallel-group studyPrimary study endpointClinical Trials RegistryMaximum serum concentrationLast quantifiable concentrationBiosimilar candidateConfidence intervalsConcentration-time curvePK similarityAdverse eventsGlycemic controlStudy endpointTrials RegistryImmunogenicity dataComparable safety
2022
P‐Glycoprotein and Breast Cancer Resistance Protein Transporter Inhibition by Cyclosporine and Quinidine on the Pharmacokinetics of Oral Rimegepant in Healthy Subjects
Bhardwaj R, Collins J, Stringfellow J, Madonia J, Anderson M, Finley J, Stock D, Coric V, Croop R, Bertz R. P‐Glycoprotein and Breast Cancer Resistance Protein Transporter Inhibition by Cyclosporine and Quinidine on the Pharmacokinetics of Oral Rimegepant in Healthy Subjects. Clinical Pharmacology In Drug Development 2022, 11: 889-897. PMID: 35304977, PMCID: PMC9311059, DOI: 10.1002/cpdd.1088.Peer-Reviewed Original ResearchConceptsBreast cancer resistance protein transporterPlasma concentration-time curveSingle oral doseGeometric mean ratiosConcentration-time curveP-glycoproteinOral doseHealthy subjectsSmall-molecule calcitonin gene-related peptide receptor antagonistCalcitonin gene-related peptide receptor antagonistStrong P-glycoprotein inhibitorBreast cancer resistance protein (BCRP) inhibitionPeptide receptor antagonistTime 0Mean ratioP-glycoprotein inhibitorsP-glycoprotein transporterConcomitant administrationCrossover studyReceptor antagonistPreventive treatmentCyclosporineCoadministrationTransporter inhibitionPharmacokineticsEarly vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase IIa clinical trial study protocol
Maciel CB, Teixeira FJP, Dickinson KJ, Spana JC, Merck LH, Rabinstein AA, Sergott R, Shan G, Miao G, Peloquin CA, Busl KM, Hirsch LJ. Early vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase IIa clinical trial study protocol. Neurological Research And Practice 2022, 4: 4. PMID: 35067230, PMCID: PMC8785535, DOI: 10.1186/s42466-022-00168-x.Peer-Reviewed Original ResearchStatus epilepticusClinical trialsVigabatrin levelsClinical trial study protocolPost-cardiac arrest periodRefractory focal-onset seizuresDose-linear pharmacokineticsPrimary feasibility endpointBlinded outcome assessmentEffective adjunctive treatmentSingle loading doseTrial study protocolBrain GABA levelsCardiac arrest survivorsPilot clinical trialLast quantifiable concentrationFocal onset seizuresGABA-ergic pathwaysReports of survivorsConcentration-time curvePrimary pharmacokinetic endpointsFeasibility endpointsAggressive treatmentEligible subjectsNeuronal injury
2021
A randomized, double-blind, parallel-group phase I study comparing the pharmacokinetics, safety, and immunogenicity of LY01008, a candidate bevacizumab biosimilar, with its reference product Avastin® in healthy Chinese male subjects
Zhou R, Yang J, Liu Y, Zhang Q, Lu C, Tang K, Li X, Tang W, Gao E, Wu C, Dou C, Hu W. A randomized, double-blind, parallel-group phase I study comparing the pharmacokinetics, safety, and immunogenicity of LY01008, a candidate bevacizumab biosimilar, with its reference product Avastin® in healthy Chinese male subjects. Expert Opinion On Biological Therapy 2021, 22: 263-269. PMID: 34913787, DOI: 10.1080/14712598.2022.2019703.Peer-Reviewed Original ResearchConceptsHealthy Chinese male subjectsChinese male subjectsStudy endpointBevacizumab biosimilarPK parametersMale subjectsGMRs of AUCParallel-group studyPrimary study endpointSecondary study endpointsMaximum serum concentrationLast quantifiable concentrationFurther clinical evaluationConcentration-time curveHealthy Chinese malesInhibitors of angiogenesisAnti-cancer therapyImmunogenicity profileComparable safetySimilar immunogenicitySerum concentrationsClinical evaluationBioequivalence marginTime zeroHealthy subjectsSafety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
Arrieta AC, Neely M, Day JC, Rheingold SR, Sue PK, Muller WJ, Danziger-Isakov LA, Chu J, Yildirim I, McComsey GA, Frangoul HA, Chen TK, Statler VA, Steinbach WJ, Yin DE, Hamed K, Jones ME, Lademacher C, Desai A, Micklus K, Phillips DL, Kovanda LL, Walsh TJ. Safety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients. Antimicrobial Agents And Chemotherapy 2021, 65: 10.1128/aac.00290-21. PMID: 34031051, PMCID: PMC8284446, DOI: 10.1128/aac.00290-21.Peer-Reviewed Original ResearchConceptsPhase 1 studyPediatric patientsIsavuconazonium sulfatePlasma drug exposureDrug exposureOral administrationImmunocompromised Pediatric PatientsNew triazole agentProdrug isavuconazonium sulfateTolerability of isavuconazoleBody mass indexPopulation PK modelInvasive fungal infectionsProbability of targetTarget rangeConcentration-time curveFirst-order inputMass indexPopulation pharmacokineticsStepwise covariate modelingTriazole agentsClinical dosePK parametersLinear eliminationPatients
2019
Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment
Srinivas N, Joseph SB, Robertson K, Kincer LP, Menezes P, Adamson L, Schauer AP, Blake KH, White N, Sykes C, Luciw P, Eron JJ, Forrest A, Price R, Spudich S, Swanstrom R, Kashuba A. Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment. Clinical And Translational Science 2019, 12: 302-311. PMID: 30675981, PMCID: PMC6510381, DOI: 10.1111/cts.12620.Peer-Reviewed Original ResearchConceptsBrain tissue concentrationsCerebrospinal fluidBrain tissueRhesus macaquesNeurocognitive scoresPK/pharmacodynamic analysesPenetration of antiretroviralsTissue concentrationsExposure-response analysisConcentration-time curveAdult rhesus macaquesCSF AUCEfavirenz concentrationsPlasma AUCPharmacodynamic analysisClinical studiesTissue AUCNeurocognitive impairmentCSF samplesPharmacokinetic dataPK modelingHIVTime pointsAUCNecropsy
2018
Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships
Kip AE, del Mar Castro M, Gomez MA, Cossio A, Schellens JHM, Beijnen JH, Saravia NG, Dorlo TPC. Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure–response relationships. Journal Of Antimicrobial Chemotherapy 2018, 73: 2104-2111. PMID: 29757380, PMCID: PMC6251527, DOI: 10.1093/jac/dky143.Peer-Reviewed Original ResearchConceptsExposure-response relationshipProbability of curePopulation PK modelMiltefosine concentrationsDosing simulationsPK targetPK modelNew World cutaneous leishmaniasisPlasma concentration-time curveCutaneous leishmaniasis patientsPopulation pharmacokinetic modelLarge cohort studyPopulation pharmacokinetic modellingConcentration-time curvePlasma concentration ratioDistribution rate constantMiltefosine exposureCohort studyLeishmaniasis patientsPatient populationEffect compartmentCutaneous leishmaniasisDay 1Three-compartment modelPharmacokinetic modellingPharmacokinetic and pharmacodynamic profile of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial
Laffel LMB, Tamborlane WV, Yver A, Simons G, Wu J, Nock V, Hobson D, Hughan KS, Kaspers S, Marquard J. Pharmacokinetic and pharmacodynamic profile of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial. Diabetic Medicine 2018, 35: 1096-1104. PMID: 29655290, PMCID: PMC6099360, DOI: 10.1111/dme.13629.Peer-Reviewed Original ResearchConceptsType 2 diabetesG/24 hPharmacodynamic profileType 2Type 2 diabetes trialsSodium-glucose co-transporter-2 inhibitor empagliflozinMaximum observed plasma concentrationPlasma concentration-time curveSimilar exposure-response relationshipsDoses of empagliflozinSerious adverse eventsParallel-group studyUrinary glucose excretionSingle oral doseDrug-related eventsObserved plasma concentrationConcentration-time curveExposure-response relationshipAdjusted mean increaseAdverse eventsDiabetes (ACCORD) trialGlucose excretionInhibitor empagliflozinOral doseMean age
2017
Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis
del Mar Castro M, Gomez MA, Kip AE, Cossio A, Ortiz E, Navas A, Dorlo TP, Saravia NG. Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis. Antimicrobial Agents And Chemotherapy 2017, 61: 10.1128/aac.02198-16. PMID: 27956421, PMCID: PMC5328512, DOI: 10.1128/aac.02198-16.Peer-Reviewed Original ResearchConceptsCutaneous leishmaniasisMiltefosine concentrationsPeripheral blood mononuclear cellsInitiation of treatmentCompletion of treatmentBlood mononuclear cellsEnd of treatmentOutcome of treatmentConcentration-time curvePharmacokinetic clinical trialsClinical responsePediatric patientsPediatric populationMononuclear cellsTherapeutic regimensDrug exposureClinical trialsNoncompartmental analysisParasite eliminationTherapeutic outcomesStudy participantsMiltefosinePatientsLiquid chromatography-tandem mass spectrometryPK differences
2015
Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non–small cell lung cancer
Nayak L, DeAngelis LM, Robins HI, Govindan R, Gadgeel S, Kelly K, Rigas JR, Peereboom DM, Rosenfeld SS, Muzikansky A, Zheng M, Urban P, Abrey LE, Omuro A, Wen PY. Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non–small cell lung cancer. Cancer 2015, 121: 4165-4172. PMID: 26308485, PMCID: PMC5941922, DOI: 10.1002/cncr.29636.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerProgressive brain metastasesBrain metastasesCell lung cancerAdverse eventsStudy drugLung cancerGrade 3/4 adverse eventsMulticenter phase 2 studyNSCLC brain metastasesSteady-state distribution volumePhase 1/2 studyRecurrent brain metastasesPhase 2 studyProgression-free survivalFirst prospective studyConcentration-time curvePrimary endpointAdult patientsOverall survivalPulmonary embolismMedian agePeripheral neuropathyMedian timeProspective studyPharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia
Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey J, Glorieux FH, Portale AA, Insogna K, Carpenter TO, Peacock M. Pharmacokinetics and pharmacodynamics of a human monoclonal anti‐FGF23 antibody (KRN23) in the first multiple ascending‐dose trial treating adults with X‐linked hypophosphatemia. The Journal Of Clinical Pharmacology 2015, 56: 176-185. PMID: 26073451, PMCID: PMC5042055, DOI: 10.1002/jcph.570.Peer-Reviewed Original ResearchConceptsConcentration-time curveSerum fibroblast growth factor 23Multiple ascending dose trialFibroblast growth factor 23Ascending dose trialHuman IgG1 monoclonal antibodyLow-normal serumRecombinant human IgG1 monoclonal antibodyDihydroxyvitamin D concentrationsGlomerular filtration rateGrowth factor 23Serum inorganic phosphorusSerum Pi concentrationIgG1 monoclonal antibodyFGF23 antibodyDose adjustmentFactor 23Serum PiFiltration ratePhosphate reabsorptionBone markersKRN23D concentrationsNormal serumMonoclonal antibodies
2014
Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC).
Tagawa S, Nanus D, Posadas E, Petrylak D, Bruce J, Lim E, Peng W, Maul R, Gonzalez M, Tran N. Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2014, 32: 205-205. DOI: 10.1200/jco.2014.32.4_suppl.205.Peer-Reviewed Original ResearchDose-limiting toxicityMetastatic castration-resistant prostate cancerAbiraterone acetateExperienced dose-limiting toxicityProstate-specific antigen (PSA) declineCastration-resistant prostate cancerPhase Ib studyMaximum plasma concentrationConcentration-time curveIntolerable toxicityPSA progressionMedian timeSystemic exposurePlasma concentrationsProstate cancerIb studyPharmacokinetic parametersFurther evaluationWk 2Wk 7CohortToxicityComplementary mechanismsProportion of PtSafety
2013
Investigation of the Interactions between Methadone and Elvitegravir-Cobicistat in Subjects Receiving Chronic Methadone Maintenance
Bruce RD, Winkle P, Custodio JM, Wei X, Rhee MS, Kearney BP, Ramanathan S, Friedland GH. Investigation of the Interactions between Methadone and Elvitegravir-Cobicistat in Subjects Receiving Chronic Methadone Maintenance. Antimicrobial Agents And Chemotherapy 2013, 57: 6154-6157. PMID: 24080665, PMCID: PMC3837895, DOI: 10.1128/aac.01229-13.Peer-Reviewed Original ResearchConceptsEVG/COBIBaseline valuesEffect of elvitegravirOpioid-dependence therapiesHIV-seronegative subjectsConcentration-time curveChronic methadone maintenanceDependence therapyOpioid withdrawalMethadone pharmacokineticsDosing periodMethadone maintenanceHistorical controlsPharmacodynamic studiesPharmacokinetic parametersMethadoneCobicistatElvitegravirMean areaAUCtauPharmacodynamicsCmaxSubjectsCOBISteady-state evaluation
2010
A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High‐Fat or Low‐Fat Meal in Patients With Advanced Solid Tumors
Heath E, Chiorean E, Sweeney C, Hodge J, Lager J, Forman K, Malburg L, Arumugham T, Dar M, Suttle A, Gainer S, LoRusso P. A Phase I Study of the Pharmacokinetic and Safety Profiles of Oral Pazopanib With a High‐Fat or Low‐Fat Meal in Patients With Advanced Solid Tumors. Clinical Pharmacology & Therapeutics 2010, 88: 818-823. PMID: 20980999, DOI: 10.1038/clpt.2010.199.Peer-Reviewed Original ResearchConceptsHigh-fat mealAdvanced solid tumorsGrowth factor receptorSolid tumorsMaximum observed plasma concentrationPlasma concentration-time curvePhase IAdministration of pazopanibOral angiogenesis inhibitorVascular endothelial growth factor receptorFactor receptorEndothelial growth factor receptorLow-fat mealObserved plasma concentrationConcentration-time curvePlatelet-derived growth factor receptorDaily pazopanibOral pazopanibSafety profileSystemic exposureSingle doseSingle dosesPlasma concentrationsPazopanibFasted condition
2009
Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda
Mwesigwa J, Parikh S, McGee B, German P, Drysdale T, Kalyango JN, Clark TD, Dorsey G, Lindegardh N, Annerberg A, Rosenthal PJ, Kamya MR, Aweeka F. Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda. Antimicrobial Agents And Chemotherapy 2009, 54: 52-59. PMID: 19841149, PMCID: PMC2798532, DOI: 10.1128/aac.00679-09.Peer-Reviewed Original ResearchConceptsArtemisinin-based combination therapyUncomplicated malariaActive metaboliteConcentration-time curveWorld Health OrganizationACT regimensArtesunate-AmodiaquineLast doseArtemether-lumefantrineLevel of exposureDrug regimensVenous samplingCombination therapyUgandan childrenPK parametersPharmacokinetic dataArtemisinin derivativesPK resultsOptimum dosingRegimensLumefantrineHealth OrganizationAdultsChildrenDesethylamodiaquine
2008
Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Ramanathan R, Egorin M, Takimoto C, Remick S, Doroshow J, LoRusso P, Mulkerin D, Grem J, Hamilton A, Murgo A, Potter D, Belani C, Hayes M, Peng B, Ivy S. Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group. Journal Of Clinical Oncology 2008, 26: 563-569. PMID: 18235115, DOI: 10.1200/jco.2007.11.0304.Peer-Reviewed Original ResearchConceptsNausea/vomitingLiver dysfunctionLiver functionLD groupNational Cancer Institute Organ Dysfunction Working GroupLiver function test elevationsPlasma concentration-time curveD dose levelDose of imatinibDoses of imatinibSevere liver dysfunctionDose-limiting toxicityMild liver dysfunctionSerum total bilirubinNormal liver functionPharmacokinetics of imatinibDose-normalized areaConcentration-time curveConcentrations of imatinibImatinib doseAdvanced malignanciesImatinib exposureMaximal doseImatinib mesylateRenal excretion
2006
Interactions between Buprenorphine and Antiretrovirals. II. The Protease Inhibitors Nelfinavir, Lopinavir/Ritonavir, and Ritonavir
McCance-Katz EF, Moody DE, Smith PF, Morse GD, Friedland G, Pade P, Baker J, Alvanzo A, Jatlow P, Rainey PM. Interactions between Buprenorphine and Antiretrovirals. II. The Protease Inhibitors Nelfinavir, Lopinavir/Ritonavir, and Ritonavir. Clinical Infectious Diseases 2006, 43: s235-s246. PMID: 17109310, DOI: 10.1086/508188.Peer-Reviewed Original ResearchMeSH KeywordsAdultBuprenorphineCase-Control StudiesCohort StudiesDose-Response Relationship, DrugDrug Administration ScheduleDrug InteractionsFemaleHIV Protease InhibitorsHIV SeronegativityHumansLopinavirMaleNarcotic AntagonistsNelfinavirOpioid-Related DisordersProbabilityPyrimidinonesReference ValuesRisk AssessmentRitonavirConceptsLPV/rLopinavir/ritonavirProtease inhibitor nelfinavirOpioid dependenceAdministration of ritonavirOpioid partial agonistAdjustment of dosesHuman immunodeficiency virusConcentration-time curveHealthy control participantsPI administrationPI pharmacokineticsHIV diseaseNegative volunteersImmunodeficiency virusOpiate withdrawalDrug interactionsBuprenorphineRitonavirPartial agonistNelfinavirControl participantsPharmacokinetic studyAdministrationSignificant increase
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