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Sixty patients who were scheduled for elective surgery under general anaesthesia (30 males\/30 females) were enrolled. Patients were randomly allocated to receive one of 15 combinations of drug levels. Baseline electroencephalograms (<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>s) were recorded for 5\u00a0minutes prior to administering the drugs. Patients received a target\u2010controlled infusion at one of four predefined doses of propofol (high, 3\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>; medium, 1.5\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>; low, 0.5\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>; or no drug) and of remifentanil (high, 6 or 8\u00a0ng\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>; medium, 4\u00a0ng\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>; low, 2\u00a0ng\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>; or no drug). The occurrence of muscle rigidity, apnoea, and loss of consciousness (<jats:styled-content style=\"fixed-case\">LOC<\/jats:styled-content>) was monitored, and <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>s were recorded during the drug administration phase. Electroencephalographic approximate entropy (ApEn) and temporal linear mode complexity (<jats:styled-content style=\"fixed-case\">TLMC<\/jats:styled-content>) parameters at baseline and under steady state conditions were calculated off\u2010line. Response surfaces were developed to map the interaction between propofol and remifentanil to the probability of occurrence for quantal responses (muscle rigidity, apnoea, <jats:styled-content style=\"fixed-case\">LOC<\/jats:styled-content>) and ApEn and <jats:styled-content style=\"fixed-case\">TLMC<\/jats:styled-content> measurements. Model parameters were estimated using non\u2010linear mixed effects modelling. The response surface revealed infra\u2010additive and synergistic effects for muscle rigidity and apnoea, respectively. The effects of the combined drugs on <jats:styled-content style=\"fixed-case\">LOC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> parameters (eg, ApEn and <jats:styled-content style=\"fixed-case\">TLMC<\/jats:styled-content>) were additive. The <jats:italic>C<\/jats:italic><jats:sub>50<\/jats:sub> estimates of remifentanil (ng\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>) and propofol (\u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>) were 9.11 and 130\u00a0000 for muscle rigidity, 8.99 and 6.26 for apnoea, 13.9 and 3.04 for <jats:styled-content style=\"fixed-case\">LOC<\/jats:styled-content>, 23.4 and 10.4 for ApEn, and 14.8 and 6.51 for <jats:styled-content style=\"fixed-case\">TLMC<\/jats:styled-content>, respectively. The probability of occurrence for muscle rigidity declined when propofol was combined with remifentanil.<\/jats:p>","DOI":"10.1111\/1440-1681.12677","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T12:35:05Z","timestamp":1475843705000},"page":"30-40","source":"Crossref","is-referenced-by-count":10,"title":["Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia"],"prefix":"10.1111","volume":"44","author":[{"given":"SangMin","family":"Choe","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Pusan National University Hospital  Pusan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung\u2010Moon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Asan Medical Center University of Ulsan College of Medicine  Seoul 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