OBJECTIVE: To study the effects of ritonavir on the pharmacokinetics of sufentanil in rabbits. METHODS: 24 rabbits 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 sufentanil 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.