Abstract
We describe a method, which is both specific and rapid, for the measurement of bupivacaine concentrations in plasma using high-performance liquid chromatography. Bupivacaine plasma concentrations, pharmacokinetics and protein binding in the postoperative period were investigated in seven patients (58-77 years old) following hip surgery. Postoperative analgesia was achieved by epidural bolus injections of 25 mg bupivacaine 0.25% every 6 h. Sufficient pain relief without side-effects was obtained. Total (maximum 1.13 micrograms/ml) as well as free (maximum 0.1 microgram/ml) bupivacaine plasma concentrations remained below toxic threshold levels and no cumulation occurred. Increased protein binding in the postoperative period is reported, emphasizing the importance of measuring the free fraction in addition to the total plasma concentration. The free fraction decreased from 5.4% preoperatively to 2.7% in the postoperative period (P less than 0.05). Changes in plasma protein binding of bupivacaine and changes in plasma levels of the acute phase reactant alpha-1-acid glycoprotein were correlated (r = 0.8, P less than 0.05). Difficulties in interpreting the elimination parameters following epidural administration are discussed, leading to the conclusion that the derivation of dosage regimens from kinetic parameters following epidural administration is not warranted.
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