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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2007, Vol. 12 ›› Issue (10): 1151-1156.

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Pharmacokinetic/pharmacodynamic studies in anestheticdrug-drug interactions-a response surface model with remifentanil and sevoflurane for Chinese adult patients

YANG Lu1, YANG Ba-xian2, ZHANG Li-ping1, BI Shan-shan3, LU Wei3,4   

  1. 1Department of Anesthesiology, Third Hospital, Peking University, Beijing 100083, China;
    2Department of Anesthesiology, People's Hospital, Peking University, Beijing 100083, China;
    3Deptartment of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing 100083, China;
    4State Key Lab.of Natural and Biomimetic Drugs, Beijing 100083, China
  • Online:2007-10-26 Published:2020-11-04
  • Contact: LU Wei, male, PhD, professor.Tel:86-10-82801717 　E-mail:luwei pk @bjmu.edu.cn
  • Supported by:
    This work was supported by research grants from the National Natural S cience Foundation of China, C30528026, C30672497, and by the China Medi cal Board of New York grants 99-697 and 01-755.

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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, sixtyfive 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. $P=\frac{(Us+Ur)^{r}}{[U_{50}/I(Q)]^{r}+(Us+Ur)^{r}}$ 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.

Key words: drug-drug interactions, synergy, response-surface