2018
Pharmacokinetic/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 ResearchConceptsNeuromuscular 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
2016
Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man
Heerdt PM, Sunaga H, Owen JS, Murrell MT, Malhotra JK, Godfrey D, Steinkamp M, Savard P, Savarese JJ, Lien CA. Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man. Anesthesiology 2016, 125: 1136-1143. PMID: 27749289, DOI: 10.1097/aln.0000000000001386.Peer-Reviewed Original ResearchConceptsCardiopulmonary side effectsHistamine releaseSide effectsBlood pressureHealthy subjectsHeart rateSevoflurane/nitrous oxideDose-escalation clinical trialDynamic airway complianceNeuromuscular-blocking drugsEscalation clinical trialPlasma histamine concentrationSigmoid Emax modelClinical recoveryClinical durationAdductor pollicisTwitch depressionAirway complianceNeuromuscular blockadeClinical trialsPreclinical studiesArterial bloodEmax modelHistamine concentrationCW002
2015
Novel neuromuscular blocking drugs and antagonists
Heerdt PM, Sunaga H, Savarese JJ. Novel neuromuscular blocking drugs and antagonists. Current Opinion In Anaesthesiology 2015, 28: 403-410. PMID: 26087274, DOI: 10.1097/aco.0000000000000209.Peer-Reviewed Original ResearchMeSH KeywordsCysteineGamma-CyclodextrinsHumansIsoquinolinesNeuromuscular BlockadeNeuromuscular Nondepolarizing AgentsSugammadexConceptsMuscle relaxantsClinical trialsNeuromuscular blocking drugsNondepolarizing muscle relaxantsNew muscle relaxantsL-cysteine injectionNondepolarizing drugSugammadex reversalBlocking drugsHistamine releasePreclinical studiesComplete paralysisCysteine injectionClinical developmentCW002RelaxantsRapid reversalIntermediate durationDrugsGantacuriumTrialsInjectionDurationRocuroniumSugammadexEffect of gantacurium on evoked laryngospasm and duration of apnea in anesthetized healthy cats.
Martin-Flores M, Cheetham J, Campoy L, Sakai DM, Heerdt PM, Gleed RD. Effect of gantacurium on evoked laryngospasm and duration of apnea in anesthetized healthy cats. American Journal Of Veterinary Research 2015, 76: 216-23. PMID: 25710757, DOI: 10.2460/ajvr.76.3.216.Peer-Reviewed Original ResearchConceptsDuration of apneaHemoglobin oxygen saturationLast doseLaryngeal stimulationNeuromuscular blockOxygen saturationPelvic limbsLaryngeal mask airwayComplete neuromuscular blockDomestic shorthair catAdult domestic shorthair catsHealthy adult domestic shorthair catsMask airwayLaryngeal maskSE durationAnesthetized catsHemoglobin desaturationLaryngospasmShorthair catClinical relevanceGantacuriumHealthy catsApneaRima glottidisDose
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 ResearchConceptsNeuromuscular 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
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
2004
Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs
Heerdt PM, Kang R, The’ A, Hashim M, Mook RJ, Savarese JJ. Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs. Anesthesiology 2004, 100: 846-851. PMID: 15087619, DOI: 10.1097/00000542-200404000-00014.Peer-Reviewed Original ResearchConceptsX ED95Cardiopulmonary changesBolus dosingDirect myocardial depressionStable neuromuscular blockadeMean arterial pressurePlasma histamine concentrationCardiopulmonary side effectsNondepolarizing neuromuscularPulmonary vasoconstrictionArterial pressureCardiovascular effectsMyocardial depressionCardiopulmonary effectsHemodynamic measurementsInspiratory pressureNeuromuscular blockadePulmonary complianceAnesthetized dogsCardiopulmonary dataMale beaglesArterial bloodED95Heart rateSide effects