Original Contributions *Assistant Professor of Anesthesiology, Uni- versity of Florida †Research Scientist, University of Florida ‡Professor of Pharmaceutics, University of Florida §Assistant Professor of Anesthesiology, Uni- versity of Texas Medical Branch at Galveston Address correspondence to Dr. Gravenstein at the Department of Anesthesiology, Univer- sity of Florida College of Medicine, P.O. Box 100254, Gainesville, FL 32610 – 0254, USA. Received for publication September 25, 1997; revised manuscript accepted for publi- cation May 13, 1998. Influence of Plasma Expansion on Plasma Protein Binding of Ketorolac Dietrich Gravenstein, MD,* Ajit Suri, PhD,† Hartmut C. Derendorf, PhD,‡ A. Jay Koska, MD, PhD§ Department of Anesthesiology, University of Florida College of Medicine; and Department of Pharmaceutics, College of Pharmacy, University of Florida, Gaines- ville, FL Study Objective: To determine the effect of dilution with intravascular volume expanders commonly used by anesthesiologists on clinically relevant levels of free serum ketorolac. Design: In vitro study. Setting: Pharmaceutics laboratory of a medical college. Interventions: The effect of 6% hydroxyethylstarch, 5% albumin, 6% dextran 60, and lactated Ringer’s solution on in vitro plasma protein binding of ketorolac was investigated by ultrafiltration. The binding was studied at three different drug concentrations: low therapeutic (0.3 g/ml), high therapeutic (3 g/ml), and toxic (10 g/ml), and at two or more volume expander dilutions. Measurements and Main Results: The effect of plasma dilution on free ketorolac was consistent across all volume expanders tested and for each ketorolac concentration studied. As the plasma dilution with albumin, hydroxyethylstarch, dextran 60, or lactated Ringer’s solution increased, the unbound ketorolac also increased from 3.2% to 3.3% in undiluted plasma to 5.0% to 8.7% in 50% dilution of the plasma with the investigated expanders. Dilution of plasma by only 10% resulted in a significant, but relatively minor, increase of unbound ketorolac to 3.2% to 3.8%. Conclusion: Because of the pharmacokinetic properties of ketorolac, this pharmacokinetic interaction can be expected to have only minor effects on unbound ketorolac concentrations when ketorolac is administered after the plasma expander. When ketorolac administration is followed by rapid plasma expander infusion, a transient increase of unbound ketorolac in plasma can be expected. © 1998 by Elsevier Science Inc. Keywords: Albumin; dextran 60; hydroxyethylstarch; ketorolac; plasma; protein binding; Ringer’s solution, lactated. Introduction Ketorolac is a potent analgesic and member of the nonsteroidal anti-inflamma- tory drug (NSAID) class. Its therapeutic advantages over opioid analgesic drugs are that it is nonsedating, it is not associated with pruritis, nausea, respiratory depression or alteration of the carbon dioxide (CO 2 )–minute ventilation response curve, urinary retention or ileus, and it has opioid-sparing qualities. Like other NSAIDs, however, ketorolac has been implicated as a contributing Journal of Clinical Anesthesia 10:464 – 468, 1998 © 1998 Elsevier Science Inc. All rights reserved. 0952-8180/98/$19.00 655 Avenue of the Americas, New York, NY 10010 PII S0952-8180(98)00064-6