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

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AUTHORS: Gurunathan, Usha FANZCA et al

Anesthesia & Analgesia: September 2019 – Volume 129 – Issue 3 – p 701-708
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.

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