title: Synergism between rocuronium and cisatracurium: comparison of the Minto and Greco interaction models.
abstract: BACKGROUND
  This study was conducted to investigate the pharmacodynamic interaction between rocuronium and cisatracurium using the response surface model, which is not subject to the limitations of traditional isobolographic analysis.
  
  
  METHODS
  One hundred and twenty patients were randomly allocated to receive one of the fifteen predefined combinations of rocuronium and cisatracurium. To study single drugs, cisatracurium 0.2, 0.15, or 0.1 mg/kg or rocuronium 0.8, 0.6 or 0.4 mg/kg doses were administered alone. To study the pharmacodynamic interaction, drugs were applied in three types of combination ratio, i.e., half dose of each drug alone, 75% of each single dose of rocuronium and 25% of each single dose of cisatracurium, and vice versa. Train-of-four (TOF) ratio and T1% (first twitch of the TOF presented as percentage compared to the initial T1) were used as pharmacodynamic endpoints, and the Greco and Minto models were used as surface interaction models.
  
  
  RESULTS
  The interaction term α of the Greco model for TOF ratio and T1% measurements showed synergism with values of 0.977 and 1.12, respectively. Application of the Minto model resulted in U50 (θ) values (normalized unit of concentration that produces 50% of the maximal effect in the 0 < θ < 1 region) less than 1 for both TOF ratio and T1% measurements, indicating that rocuronium and cisatracurium exhibit synergism.
  
  
  CONCLUSIONS
  Response surface modeling of the interaction between rocuronium and cisatracurium, based on considerations of their effects on muscle relaxation as measured by TOF ratio and T1%, indicated that the two drugs show considerable synergism.
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University Hospital, Busan, Korea.
authors.forename: Soeun
authors.identifier: 0000-0002-4009-6321
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University Hospital, Busan, Korea.; Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University Hospital, Busan, Korea.; Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Hae-Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea.; Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Tae Kyun
authors.identifier: 0000-0002-4790-896X
authors.initials: TK
authors.lastname: Kim
keywords: Cisatracurium; Drug interactions; Pharmacology; Rocuronium