Population Pharmacokinetics of Periarticular Ketorolac in Adult Patients Undergoing Total Hip or Total Knee Replacement Surgery

BACKGROUND: Ketorolac tromethamine has been used for joint infiltration by the orthopedic surgeons as a part of postoperative multimodal analgesia. The objective of this study is to investigate the pharmacokinetic properties of S (−) and R (+) enantiomers of ketorolac in adult patients undergoing total hip (THA) and knee arthroplasty (TKA). METHODS: Adult patients with normal preoperative renal function received a periarticular infiltration of 30 mg of ketorolac tromethamine along with 100 mL of 0.2% ropivacaine and 1 mg of epinephrine at the end of their THA or TKA surgery. Blood samples were taken from a venous cannula at various time points after infiltration. Pharmacokinetic modeling was performed using PMetrics 1.5.0. RESULTS: From 18 participants, 104 samples were analyzed. The peak plasma concentration for S (−) ketorolac was found to be lower than that of R (+) ketorolac, for both THA (0.19–1.22 mg/L vs 0.39–1.63 mg/L, respectively) and TKA (0.28–0.60 mg/L vs 0.48–0.88 mg/L, respectively). The clearance of the S (−) ketorolac enantiomer was higher than R (+) ketorolac (4.50 ± 2.27 vs 1.40 ± 0.694 L/h, respectively). CONCLUSIONS: Our study demonstrates that with periarticular infiltration, S (−) ketorolac was observed to have increased clearance rate and highly variable volume of distribution and lower peak plasma concentration compared to R (+) ketorolac. Accepted for publication February 28, 2018. Funding: This project was supported by research funding from the Department of Anaesthesia and Perfusion Services at the Prince Charles Hospital, Brisbane, Australia. The authors declare no conflicts of interest. Clinical trial number and registry: Australian New Zealand Clinical Trials Registry (ACTRN12613000923763). Reprints will not be available from the authors. Address correspondence to Usha Gurunathan, FANZCA, Department of Anaesthesia & Perfusion Services, The Prince Charles Hospital, Rode Rd, Chermside, QLD 4032, Australia. Address e-mail to usha.gurunathan@health.qld.gov.au. © 2018 International Anesthesia Research Society

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