1993
The effect of L-dopa infusions with and without phenylalanine challenges in parkinsonian patients: plasma and ventricular CSF L-dopa levels and clinical responses.
Woodward WR, Olanow CW, Beckner RM, Hauser RA, Gauger LL, Cedarbaum JM, Nutt JG. The effect of L-dopa infusions with and without phenylalanine challenges in parkinsonian patients: plasma and ventricular CSF L-dopa levels and clinical responses. Neurology 1993, 43: 1704-8. PMID: 8414016, DOI: 10.1212/wnl.43.9.1704.Peer-Reviewed Original ResearchConceptsL-DOPAMotor responseLarge neutral amino acidsVentricular CSF concentrationsAdvanced Parkinson's diseaseL-DOPA infusionL-DOPA levelsClinical responseParkinsonian patientsCSF concentrationsOral administrationNeutral amino acidsParkinson's diseaseInfusionPatientsPhenylalanine challengeReliable predictorCSFVDiseaseBrainDurationResponsePlasmaLevelsAdministrationAdministration of the new COMT inhibitor OR‐611 increases striatal uptake of fluorodopa
Guttman M, Léger G, Reches A, Evans A, Kuwabara H, Cedarbaum JM, Gjedde A. Administration of the new COMT inhibitor OR‐611 increases striatal uptake of fluorodopa. Movement Disorders 1993, 8: 298-304. PMID: 8341294, DOI: 10.1002/mds.870080308.Peer-Reviewed Original ResearchConceptsPositron emission tomographyNew COMT inhibitorL-DOPACOMT inhibitorsTreatment of patientsStriatal uptakeBrain uptakeBrain 6Cynomolgus monkeysParkinson's diseaseL-dopa analogEmission tomographyPromising agentSame animalsPET measurementsDiseaseMetabolismInhibitorsControl statePretreatmentPatientsFluorodopaAdjunctAdministrationUptake
1991
Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson's disease.
Cedarbaum J, Olanow CW. Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson's disease. Neurology 1991, 41: 1567-70. PMID: 1922797, DOI: 10.1212/wnl.41.10.1567.Peer-Reviewed Original ResearchConceptsAdvanced Parkinson's diseaseDopamine sulfateParkinson's diseaseDopamine sulfate levelsLevodopa/carbidopaTime of transplantationPeak plasma concentrationAvailability of dopamineVentricular cerebrospinal fluidSulfate levelsClinical improvementMotor fluctuationsOmmaya reservoirSingle doseExogenous levodopaParkinsonian brainMotor functionPlasma concentrationsLateral ventricleCerebrospinal fluidAdrenal medullaLevodopaPatientsDiseaseDopamineReduction of Circulating 3-O-Methyldopa by Inhibition of Gatechol-O-Methyltransferase With OR-611 and OR-462 in Cynomolgus Monkeys: Implications for the Treatment of Parkinson's Disease.
Cedarbaum J, Leger G, Guttman M. Reduction of Circulating 3-O-Methyldopa by Inhibition of Gatechol-O-Methyltransferase With OR-611 and OR-462 in Cynomolgus Monkeys: Implications for the Treatment of Parkinson's Disease. Clinical Neuropharmacology 1991, 14: 330. PMID: 1913700, DOI: 10.1097/00002826-199108000-00005.Peer-Reviewed Original ResearchL-Deprenyl (Selegiline) Added to Sinemet CR in the Management of Parkinson's Disease Patients With Motor Response Fluctuations.
Cedarbaum JM, Toy LH, Green-Parsons A. L-Deprenyl (Selegiline) Added to Sinemet CR in the Management of Parkinson's Disease Patients With Motor Response Fluctuations. Clinical Neuropharmacology 1991, 14: 228. PMID: 1906374, DOI: 10.1097/00002826-199106000-00005.Peer-Reviewed Original ResearchConceptsSinemet CRParkinson's diseaseResponse fluctuationsDisease patientsL-deprenylMean interdose intervalTherapeutic response fluctuationsAdvanced Parkinson's diseaseMotor response fluctuationsParkinson's disease patientsLevodopa intakeMotor fluctuationsInterdose intervalTreatment regimensPatientsSignificant reductionDeprenylDiseaseRegimensDyskinesiaImproved controlTemporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease
Olanow CW, Gauger LL, Cedarbaum JM. Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease. Annals Of Neurology 1991, 29: 556-559. PMID: 1859185, DOI: 10.1002/ana.410290516.Peer-Reviewed Original ResearchConceptsVentricular cerebrospinal fluidCerebrospinal fluidParkinson's diseasePlasma levodopa concentrationsAdvanced Parkinson's diseaseCerebrospinal fluid pharmacokineticsPharmacokinetics of levodopaCentral nervous systemLevodopa levelsOmmaya reservoirClinical effectsLevodopa effectsParkinsonian patientsLevodopa concentrationsHomovanillic acidNervous systemDrug concentrationsLevodopaDiseaseMotor performancePatientsTime coursePharmacokineticsTemporal relationshipNucleus transplantation"Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson's disease.
Cedarbaum JM, Gandy SE, McDowell FH. "Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson's disease. Neurology 1991, 41: 622-9. PMID: 2027475, DOI: 10.1212/wnl.41.5.622.Peer-Reviewed Original ResearchConceptsMotor response fluctuationsLevodopa therapyLevodopa treatmentDisease clinicResponse fluctuationsParkinson's disease clinicDevelopment of dyskinesiaHistory of patientsTiming of initiationPatient populationDisease onsetParkinson's diseaseDyskinesiaYounger ageDementiaPatientsTherapyAdverse consequencesTreatmentDiseaseGreater proportionInitiationDisease diagnosisClinicDiagnosis
1990
Effect of Nitecapone (OR-462) on the Pharmacokinetics of Levodopa and 3-O-Methyldopa Formation in Cynomolgus Monkeys.
Cedarbaum JM, Léger G, Reches A, Guttman M. Effect of Nitecapone (OR-462) on the Pharmacokinetics of Levodopa and 3-O-Methyldopa Formation in Cynomolgus Monkeys. Clinical Neuropharmacology 1990, 13: 544. PMID: 2276119, DOI: 10.1097/00002826-199012000-00006.Peer-Reviewed Original ResearchConceptsCynomolgus monkeysEffect of nitecaponePeripheral COMT inhibitorSingle-dose studyPharmacokinetics of levodopaBlood-brain barrierConcentration-time curveLevodopa administrationPlasma pharmacokineticsCOMT inhibitorsAdverse physiological effectsFurther inhibitionLevodopaDoseNitecaponePhysiological effectsMonkeysPharmacokineticsNovel inhibitorsInhibitorsInhibitionCarbidopaAdministrationResults of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR)
Cedarbaum JM, Silvestri M, Clark M, Toy L, Harts A, Green-Parsons A, McDowell FH. Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR). Journal Of Neural Transmission: Parkinson's Disease A And Dementia Section 1990, 2: 205-213. PMID: 2257060, DOI: 10.1007/bf02257651.Peer-Reviewed Original ResearchConceptsStandard SinemetMotor response fluctuationsResponse fluctuationsSinemet CRDisease patientsControlled-release levodopa/carbidopaLevodopa/carbidopaLong-term treatmentParkinson's disease patientsLong-term managementAntiparkinson effectEligible patientsMost patientsMedication dosesInterdose intervalClinical trialsParkinson's diseaseUseful adjunctPatientsSinemetDiseaseYearsCarbidopaAdjunctDoseSustained enteral administration of levodopa increases and interrupted infusion decreases levodopa dose requirements.
Cedarbaum J, Silvestri M, Kutt H. Sustained enteral administration of levodopa increases and interrupted infusion decreases levodopa dose requirements. Neurology 1990, 40: 995-7. PMID: 2345621, DOI: 10.1212/wnl.40.6.995.Peer-Reviewed Original ResearchConceptsInterrupted infusionTherapeutic response fluctuationsStriatal dopamine receptorsContinuous enteral infusionLevodopa dose requirementEnteral administrationEnteral infusionContinuous infusionDopamine receptorsInfusion rateParkinson's diseaseDose requirementsInfusionResponse fluctuationsMotor performanceLevodopaDiseasePatientsAdministrationReceptorsL-Deprenyl, Levodopa Pharmacokinetics, and Response Fluctuations in Parkinson's Disease.
Cedarbaum JM, Silvestri M, Clark M, Harts A, Kutt H. L-Deprenyl, Levodopa Pharmacokinetics, and Response Fluctuations in Parkinson's Disease. Clinical Neuropharmacology 1990, 13: 29. PMID: 2106391, DOI: 10.1097/00002826-199002000-00003.Peer-Reviewed Original ResearchConceptsParkinson's diseaseResponse fluctuationsL-deprenylTherapeutic response fluctuationsTotal levodopa doseOpen-label trialPlasma levodopa concentrationsPlasma levodopa levelsEffect of deprenylWeeks of treatmentDaily levodopaLevodopa doseLevodopa pharmacokineticsPeripheral pharmacokineticsAction of MAOLevodopa treatmentMost patientsDOPAC levelsLevodopa levelsDopaminergic activityLevodopa concentrationsMild endDose failureTherapeutic actionPatientsPharmacokinetic and Pharmacodynamic Considerations in Management of Motor Response Fluctuations in Parkinson's Disease
Cedarbaum J. Pharmacokinetic and Pharmacodynamic Considerations in Management of Motor Response Fluctuations in Parkinson's Disease. Neurologic Clinics 1990, 8: 31-49. PMID: 2181267, DOI: 10.1016/s0733-8619(18)30372-4.Peer-Reviewed Original ResearchConceptsMotor response fluctuationsResponse fluctuationsLevodopa-related fluctuationsSynthetic dopamine agonistsPlasma levodopa levelsMajority of patientsPharmacokinetics of levodopaSuch treatment approachesBrain dopaminergic activityLong-term treatmentBrain dopamine levelsRapid systemic clearanceAnti-Parkinson agentsLevodopa levelsDopamine agonistsPharmacodynamic consequencesPharmacodynamic considerationsSystemic clearanceAdvanced PDDopamine levelsDopaminergic activityTherapeutic approachesParkinson's diseaseTreatment approachesGalenic formulationSustained‐release (+)‐PHNO [MK‐458 (HPMC)] in the treatment of Parkinson's disease: Evidence for tolerance to a selective D2‐receptor agonist administered as a long‐acting formulation
Cedarbaum J, Clark M, Toy L, Green‐Parsons A. Sustained‐release (+)‐PHNO [MK‐458 (HPMC)] in the treatment of Parkinson's disease: Evidence for tolerance to a selective D2‐receptor agonist administered as a long‐acting formulation. Movement Disorders 1990, 5: 298-303. PMID: 1979657, DOI: 10.1002/mds.870050407.Peer-Reviewed Original ResearchConceptsMK-458Disease patientsSelective D2 receptor agonistPostsynaptic dopamine receptorsMotor response fluctuationsD2 receptor agonistParkinson's disease patientsSustained-release formAdjunctive therapyD2 agonistDopamine receptorsSinemetParkinson's diseaseAgonistsResponse fluctuationsProgressive lossPatientsWeeksDiseaseDosageReduced sensitivityDaysTherapyReceptors
1989
A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100).
Cedarbaum JM, Kutt H, McDowell FH. A pharmacokinetic and pharmacodynamic comparison of Sinemet CR (50/200) and standard Sinemet (25/100). Neurology 1989, 39: 38-44; discussion 59. PMID: 2586762.Peer-Reviewed Original ResearchConceptsSinemet CRLevodopa levelsNew controlled-release formulationStandard Sinemet 25/100Advanced Parkinson's diseasePlasma levodopa levelsBioavailability of levodopaClinical observation studyAntiparkinsonian effectsLevodopa intakeSinemet 25/100Standard SinemetPharmacodynamic comparisonMedication dosesInterdose intervalParkinson's diseaseCR preparationControlled-release formulationLevodopaMotor performanceCarbidopaObservation studyDiseaseProlongationSinemetThe Promise and Limitations of Controlled-Release Oral Levodopa Administration.
Cedarbaum JM. The Promise and Limitations of Controlled-Release Oral Levodopa Administration. Clinical Neuropharmacology 1989, 12: 147. PMID: 2663145, DOI: 10.1097/00002826-198906000-00001.Peer-Reviewed Original ResearchA double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance.
Cedarbaum JM, Hoey M, McDowell FH. A double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance. Journal Of Neurology Neurosurgery & Psychiatry 1989, 52: 207. PMID: 2649640, PMCID: PMC1032507, DOI: 10.1136/jnnp.52.2.207.Peer-Reviewed Original ResearchConceptsStandard Sinemet 25/100Sinemet 25/100Sinemet CR4Controlled-release levodopa/carbidopaDouble-blind crossover comparisonDaily medication dosesDouble-blind partMean interdose intervalLevodopa/carbidopaAntiparkinson effectMedication dosesInterdose intervalSevere dyskinesiaCrossover comparisonCrossover trialParkinsonian patientsTherapeutic responseMedication administrationMotor functionAntiparkinsonian agentsParkinson's diseaseOpen treatmentMotor responsePatientsMotor performance
1988
Clinical significance of the relationship between O-methyldopa levels and levodopa intake.
Cedarbaum J, Kutt H, McDowell F. Clinical significance of the relationship between O-methyldopa levels and levodopa intake. Neurology 1988, 38: 533-6. PMID: 3352906, DOI: 10.1212/wnl.38.4.533.Peer-Reviewed Original ResearchConceptsDaily intakeRecent clinical trialsMean daily intakeTotal daily intakeLevodopa intakeStandard SinemetClinical responseLevodopa preparationsBrain uptakeClinical trialsPlasma concentrationsClinical significanceBlood samplingLevodopaTherapeutic efficacyMethyldopa levelsControlled-release formulationPatientsIntakeTime curveAUCSinemetLevelsTrialsControlled-Release Levodopa/Carbidopa III: Sinemet CR5 Treatment of Response Fluctuations in Parkinson's Disease.
Cedarbaum JM, Hoey M, Kutt H, McDowell FH. Controlled-Release Levodopa/Carbidopa III: Sinemet CR5 Treatment of Response Fluctuations in Parkinson's Disease. Clinical Neuropharmacology 1988, 11: 168. PMID: 3378225, DOI: 10.1097/00002826-198804000-00008.Peer-Reviewed Original ResearchConceptsSinemet CR4Parkinson's diseasePeak plasma levodopa concentrationResponse fluctuationsOpen-label studyAdvanced Parkinson's diseasePlasma levodopa concentrationsStandard SinemetInterdose intervalDaily dosesTherapeutic responseLevodopa concentrationsSame patientLabel studyDiseaseRelative bioavailabilityPatientsGreater delayTreatmentSinemetLevodopaDoses
1987
Controlled-release levodopa/carbidopa. II. Sinemet CR4 treatment of response fluctuations in Parkinson's disease.
Cedarbaum J, Breck L, Kutt H, McDowell F. Controlled-release levodopa/carbidopa. II. Sinemet CR4 treatment of response fluctuations in Parkinson's disease. Neurology 1987, 37: 1607-12. PMID: 3658164, DOI: 10.1212/wnl.37.10.1607-a.Peer-Reviewed Original ResearchConceptsSinemet CR4Interdose intervalParkinson's diseaseResponse fluctuationsTherapeutic response fluctuationsOpen-label trialPlasma levodopa levelsSlow-release preparationAntiparkinsonian effectsStandard levodopaLevodopa dosesLevodopa preparationsLevodopa levelsDaily dosesRelease preparationDiseaseLevodopaDosesProlongationTreatmentOverall benefitSinemetPatientsSlight reductionControlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease.
Cedarbaum J, Breck L, Kutt H, McDowell F. Controlled-release levodopa/carbidopa. I. Sinemet CR3 treatment of response fluctuations in Parkinson's disease. Neurology 1987, 37: 233-41. PMID: 3808304, DOI: 10.1212/wnl.37.2.233.Peer-Reviewed Original ResearchConceptsPlasma levodopa levelsLevodopa levelsResponse fluctuationsParkinson's diseaseControlled-release carbidopa/levodopaCarbidopa/levodopaOpen-label trialBioavailability of levodopaStandard SinemetDisability scoresLevodopa preparationsInterdose intervalDaily dosesParkinson's patientsControlled-release formulationClinical performanceDiseaseLevodopaDay consistencyOverall benefitSinemetPatientsDosesTrialsWeeks