TY - JOUR
T1 - Influence of plasma expansion on plasma protein binding of ketorolac
AU - Gravenstein, Dietrich
AU - Suri, Ajit
AU - Derendorf, Hartmut C.
AU - Koska, A. Jay
PY - 1998/9
Y1 - 1998/9
N2 - 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 μg/ml), high therapeutic (3 μg/ml), and toxic (10 μg/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.
AB - 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 μg/ml), high therapeutic (3 μg/ml), and toxic (10 μg/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.
KW - Albumin
KW - Dextran 60
KW - Hydroxyethylstarch
KW - Ketorolac
KW - Plasma
KW - Protein binding
KW - Ringer's solution, lactated
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U2 - 10.1016/S0952-8180(98)00064-6
DO - 10.1016/S0952-8180(98)00064-6
M3 - Article
C2 - 9793809
AN - SCOPUS:0032168162
SN - 0952-8180
VL - 10
SP - 464
EP - 468
JO - Journal of Clinical Anesthesia
JF - Journal of Clinical Anesthesia
IS - 6
ER -