Pharmacokinetic/pharmacodynamic studies in anestheticdrug-drug interactions——a response surface model with remifentanil and sevoflurane for Chinese adult patients
- VernacularTitle:药物动力学/药效动力学在研究药物相互作用中的应用——反应曲面模型法研究瑞芬太尼与七氟醚联合应用
- Author:
Lu YANG
;
Baxian YANG
;
Liping ZHANG
;
Shanshan BI
;
Wei LU
- Publication Type:Journal Article
- Keywords:
drug-drug interactions;
synergy;
response-surface
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2007;12(10):1151-1156
- CountryChina
- Language:Chinese
-
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.
