Usha Gurunathan1, Suzanne L Parker2, Richard Maguire1, Dale Ramdath1, Manu Bijoor1, Steven C Wallis2, Jason A Roberts2,3,4. 1. From the Prince Charles Hospital & The University of Queensland, Brisbane, Queensland, Australia. 2. Faculty of Medicine, University of Queensland Centre for Clinical Research. 3. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia. 4. Department of Pharmacy and Intensive Care Unit, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia.
Abstract
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.
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.