Effects of Ritonavir on the Pharmacokinetics of Sufentanil in Rabbits / 中国药房

ABSTRACT

OBJECTIVE:To study the effects of ritonavir on the pharmacokinetics of sufentanil in rabbits. METHODS:24 rab-bits were randomly divided into 2 groups,with 12 rabbits in each group. Trial group was given ritonavir 10 mg/kg by gavage and then injected sufentanil 2 μg/kg intravenously after 5 min. Control group was given equal volume of normal saline by gavage and then injected sufentanil 2 μg/kg intravenously. Arterial blood samples 0.3 ml were taken before gavage and 0,0.25,0.5,1,2,3, 4,6,8,10,12,14,24 h after intravenous administration. The plasma concentrations of sufentanil were determined by LC-MS/MS,and DAS 2.0 software was adopted to calculate pharmacokinetic parameters. RESULTS:The pharmacokinetic change of sufen-tanil conformed to two-compartment model in 2 groups. The pharmacokinetic parameters of sufentanil in control group vs. trial group were that t1/2 were(22.0±6.59)and(26.4±1.41)h;MRT0-24 h were(8.6±2.08)and(12.1±3.70)h;AUC0-∞ were(16.1± 5.17)and(38.1±12.95)mg·h/L,respectively. There was statistical significance in MRT0-24 h and AUC0-∞ between 2 groups(P<0.05). CONCLUSIONS:Ritonavir can elevate distribution of sufentanil in rabbits,and prolong retention time of sufentanil.