2018
Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine.
Savarese JJ, Sunaga H, McGilvra JD, Belmont MR, Murrell MT, Jeannotte E, Cooke FE, Wastila WB, Heerdt PM. Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine. Anesthesiology 2018, 129: 970-988. PMID: 30212413, DOI: 10.1097/aln.0000000000002408.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCysteineHeart RateHumansMacaca mulattaMaleModels, AnimalNeuromuscular BlockadeNeuromuscular Blocking AgentsConceptsNeuromuscular blocking agentsMean arterial pressureBlocking agentArterial pressureNeuromuscular blockadeHeart rateNew neuromuscular blocking agentRhesus monkeysNondepolarizing neuromuscular blocking agentDuration of actionStudy of bolusCirculatory effectsPreclinical pharmacologyControl infusionInstitutional Animal CareED95Large dosesSpontaneous recoveryGantacuriumDose ratioL-cysteineInfusionBolusUse CommitteeRecovery intervalPharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers
Kaullen JD, Owen JS, Brouwer KLR, Heerdt PM, Lien CA, Savarese JJ, Schmith VD. Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers. Anesthesiology 2018, 128: 1107-1116. PMID: 29494403, PMCID: PMC5953789, DOI: 10.1097/aln.0000000000002157.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCohort StudiesFemaleHealthy VolunteersHumansIsoquinolinesMaleMiddle AgedModels, BiologicalNeuromuscular Blocking AgentsYoung AdultConceptsNeuromuscular blocking agentsBlocking agentRapid onsetPharmacodynamic modelDifferent dose cohortsMuscle twitch heightOffset of effectSingle ascending dosePharmacokinetic/Pharmacodynamic ModelArterial plasma concentrationsIntermediate durationPlasma drug concentration dataSigmoid Emax modelDose-response studyDrug concentration dataConcentration-time dataLow interindividual variabilityDose cohortsED95 dosesAscending dosePredictable pharmacokineticsSevoflurane anesthesiaPopulation pharmacokineticsSingle dosesTwitch height
2014
Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.
Diaz LL, Zhang J, Heerdt PM. Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits. Journal Of The American Association For Laboratory Animal Science 2014, 53: 283-9. PMID: 24827571, PMCID: PMC4128567.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtracuriumBlood PressureCross-Over StudiesHeart RateIsofluraneIsoquinolinesMaleNeuromuscular Blocking AgentsPancuroniumRabbitsConceptsNeuromuscular blocking drugsRecovery indexNew Zealand white rabbitsPotential side effectsCross-over designZealand white rabbitsComparative PharmacodynamicsBlocking drugsPharmacologic reversalMuscle twitchCisatracuriumPancuroniumAnesthetized rabbitsSide effectsCW002Cholinergic manipulationsSurvival proceduresSimilar onsetWhite rabbitsEffective doseSurvival studiesLonger durationDrugsRabbitsTime course
2011
Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles
Heerdt PM, Wagner CL, DeMais M, Savarese JJ. Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles. Journal Of Pharmacological And Toxicological Methods 2011, 64: 111-118. PMID: 21440649, DOI: 10.1016/j.vascn.2011.03.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCardiac OutputDogsDrug Evaluation, PreclinicalMaleMonitoring, PhysiologicNeuromuscular Blocking AgentsTime FactorsConceptsCardiac outputAortic blood flowDrug-induced changesBlood flowAcute drug-induced changesNoninvasive cardiac output monitoringNon-invasive measurementOpen-chest beaglesNeuromuscular blocking drugsPreclinical drug evaluationCardiac output monitoringDrug evaluation studiesML/minSimultaneous CO measurementsBlocking drugsAcute alterationsAortic rootPreclinical screeningChest instrumentationNICOMCO measurementsOutput monitoringDrug evaluationInvasive measurementsInvasive instrumentation
2010
Rapid Chemical Antagonism of Neuromuscular Blockade by l-Cysteine Adduction to and Inactivation of the Olefinic (Double-bonded) Isoquinolinium Diester Compounds Gantacurium (AV430A), CW 002, and CW 011
Savarese JJ, McGilvra JD, Sunaga H, Belmont MR, Van Ornum SG, Savard PM, Heerdt PM. Rapid Chemical Antagonism of Neuromuscular Blockade by l-Cysteine Adduction to and Inactivation of the Olefinic (Double-bonded) Isoquinolinium Diester Compounds Gantacurium (AV430A), CW 002, and CW 011. Anesthesiology 2010, 113: 58-73. PMID: 20526187, DOI: 10.1097/aln.0b013e3181dc1b5b.Peer-Reviewed Original ResearchMeSH KeywordsAlkenesAnimalsAtracuriumChemical PhenomenaCholinesterase InhibitorsChromatography, High Pressure LiquidCysteineDose-Response Relationship, DrugDrug InteractionsEdrophoniumHaplorhiniIsoquinolinesMacaca mulattaMaleMaleatesNeostigmineNeuromuscular BlockadeNeuromuscular Blocking AgentsStructure-Activity RelationshipConceptsDuration of blockED95 dosesNeuromuscular blockadeNeuromuscular blockersNovel agentsTwitch inhibitionCysteine adductionGantacuriumExogenous L-cysteineIntermediate durationAdductionL-cysteineED95Preliminary dataBlockadeAntagonismChemical antagonismHigh-performance liquid chromatographyDurationMinRapid adductionAdduction productsCisatracuriumLiquid chromatographyBlockersCysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs
Sunaga H, Malhotra JK, Yoon E, Savarese JJ, Heerdt PM. Cysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs. Anesthesiology 2010, 112: 900-909. PMID: 20234310, DOI: 10.1097/aln.0b013e3181d31f8c.Peer-Reviewed Original ResearchConceptsOrgan toxicityHeart rateIsoflurane-nitrous oxide anesthesiaAcute cardiovascular effectsNeuromuscular blocking drugsDose-response relationshipDose-dependent mannerEndogenous L-cysteineCardiovascular effectsHemodynamic effectsMedian durationArterial pressureBlood pressureBlocking drugsHistologic evidenceNeuromuscular blockadeOxide anesthesiaTwitch recoveryMuscle recoveryHistopathologic analysisMuscle twitchLarge doseCW002Additional groupDosePharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs
Heerdt PM, Malhotra JK, Pan BY, Sunaga H, Savarese JJ. Pharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs. Anesthesiology 2010, 112: 910-916. PMID: 20234311, DOI: 10.1097/aln.0b013e3181d31f71.Peer-Reviewed Original ResearchConceptsX ED95Neuromuscular blocking drugsCardiopulmonary side effectsVascular resistanceArterial pressureBlocking drugsCardiac outputHistamine releaseSide effectsMean pulmonary artery pressurePulmonary artery pressurePulmonary vascular resistanceSystemic vascular resistanceMean arterial pressurePulmonary arterial pressureArtery pressureHemodynamic effectsPulmonary complianceVentricular contractilityInspiratory pressureNeuromuscular blockadeVentricular pressureED95Large dosesCW002