Population Pharmacokinetic and Pharmacodynamic Model of Propofol in Patients With Chronic Kidney Disease

Abstract Propofol is a commonly used intravenous anesthetic. Although the kidney plays a minor role in elimination, pharmacokinetics (PK) and pharmacodynamics (PD) have been found to be significantly affected in patients with chronic kidney disease (CKD). The study was a prospective, single‐centre study in CKD patients undergoing surgery under general anaesthesia. A total of 9–10 blood samples were collected from each of 38 patients at prespecified sampling time points for propofol quantification. Time to loss of consciousness and time to eye opening were recorded, along with the bispectral index (BIS), as PD endpoints. The concentration time profile (287 samples) and BIS data from 35 patients were included in model development. Creatinine clearance was identified as an important covariate affecting the PK model. Stage 3 and 4 patients achieved higher plasma concentrations at the same induction and maintenance propofol doses and tended to have lower BIS. The propofol C max was higher in stage 4 patients than in stages 1 or 2. The average concentration at LOC was significantly higher in stage 4 (6.61 ± 6.28 µg/mL) as compared to stages 1 (2.06 ± 1.69 µg/mL) or stage 2 (1.64 ± 1.77 µg/mL). Average time to eye opening was also higher in stages 3 and 4 (12.9 ± 4.7 and 9.5 ± 3.1 min, respectively) as compared to stages 1 and 2 (7 ± 3.2 and 7.9 ± 2.4 min, respectively). The moderate‐severe renal impairment status decreases the requirement of the induction dose of propofol to achieve surgical anesthesia compared to those with normal creatinine clearance. Prolonged clearance also leads to prolonged emergence from anesthesia.