Pharmacokinetic/pharmacodynamic studies in anestheticdrug-drug interactions——a response surface model with remifentanil and sevoflurane for Chinese adult patients / 中国临床药理学与治疗学

ABSTRACT

AIM: To determine the interactions with response-surface modeling methodologies when sevoflurane (Sevo) and remifentanil (Remi) were administered simultaneously. METHODS: (1) Patients, Study design and drug delivery Based on parallel slices design, sixty-five patients were randomly assigned to inhale a specific end-tidal concentration of sevoflurane (0.3% to 3.4%), with different level of remifentanil (0-10 ng/mL). The responses to laryngoscopy were observed for each given concentration pair. (2) Pharmacokinetic/pharmacodynamic analysis with response surface mode The probability of no response (P) was assessed in the modeling process as below. P=(Us+Ur)r/[U50/I(Q)]r+(Us+Ur)r RESULTS AND DISCUSSION: NONMEM estimated average values (RSE%) of the model parameters for laryngoscopy of C50,Sevo, C50,remi, U50, r, Imax and Qmax are 1.71% (12.9), 12.4 ng/mL (19.0), 6.62 (10.6), 1.53 (8.76), 2.31 (8.23), 0.706 (2.46), respectively. The inter-individual variability (CV%) in parameter Imax and inter-occasion variability (S.D.) in this model are 12.7 and 0.0316, respectively. It is concluded that the response-surface modeling approach provided a novel method to study drug-drug interactions.