Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation.
BACKGROUND
Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia.


METHODS
Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured.


RESULTS
Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values.


CONCLUSIONS
Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.
Department of Anesthesiology, Leiden University Medical Center, The Netherlands. A.G.L.Burn@lumc.nl
A G
AG
Burm
R
R
Stienstra
R P
RP
Brouwer
B M
BM
Emanuelsson
J W
JW
van Kleef
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000577:Amides / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015360:Analgesia, Epidural; D016058:Analgesia, Patient-Controlled; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D001711:Biotransformation; D006801:Humans; D016014:Linear Models; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D010147:Pain Measurement; D010149:Postoperative Pain / Q000517:prevention & control*; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D009961:Orosomucoid; D000077212:Ropivacaine