Intraindividual and interindividual variability in the disposition of the local anesthetic ropivacaine in healthy subjects.
To predict the risk of adverse reactions to local anaesthetics used in clinical practice, it is crucial to know whether any nonlinearity exists in their pharmacokinetics. The disposition of ropivacaine, a new local anesthetic agent, was evaluated in healthy subjects on the basis of plasma levels in the concentration range obtained after regional anaesthesia. Three intravenous doses of ropivacaine hydrochloride (20, 40, and 80 mg) were given in a double-blind, randomized, complete crossover design. Analysis of variance was used to assess the importance of intra- versus interindividual variability in the basic pharmacokinetics. The mean plasma clearance (400 ml/min), volume of distribution at steady state (40 l), and terminal half-life (1.7 h) were similar, irrespective of dose. The intersubject variability for these parameters was higher than the intrasubject variability. A slight increase in free fraction (15%) with increasing dose might indicate that the lower limit for saturation of protein binding may be reached at the higher plasma levels. One subject (80 mg) reported numbness of the lower lip 2 min after the end of the infusion, which may be a sign of systemic CNS toxicity. The total and free plasma concentration was extrapolated to 1.7 and 0.08 mg/l, respectively.
Emanuelsson
B M
BM
Clinical Pharmacology, Clinical Research and Development, Astra Pain Control AB, Södertälje, Sweden.
Persson
J
J
Sandin
S
S
Alm
C
C
Gustafsson
L L
LL
D000328:Adult; D000577:Amides / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine