Effect of ciprofloxacin on the pharmacokinetics of ropivacaine.
OBJECTIVE
To assess the effect of ciprofloxacin on the pharmacokinetics of ropivacaine. METHODS. In a double-blind, randomised, cross-over study, nine healthy volunteers were treated for 2.5 days with 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 0.6 mg/kg ropivacaine intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine (3-OH-ropivacaine), and (S)-2',6'-pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 h and 24 h, respectively.


RESULTS
Ciprofloxacin decreased the mean clearance (CL) of ropivacaine by 31% (P<0.05), with a considerable inter-individual variation (range from -52% to +39%). It also decreased the area under the plasma concentration-time curve (AUC) of 3-OH-ropivacaine by 38% (P<0.05) and urinary excretion of 3-OH-ropivacaine by 27% (P<0.05). Ciprofloxacin increased the AUC of PPX by 71% (P<0.01) and urinary excretion of PPX by 97% (P<0.01).


CONCLUSIONS
Ciprofloxacin modestly decreased the mean ropivacaine CL by inhibiting the CYP1A2-mediated formation of 3-OH-ropivacaine. At the same time, the CYP3A4-mediated formation of PPX was increased. There was a marked inter-individual variation in the extent of the interaction, and, for some individuals, the concomitant use of ciprofloxacin with ropivacaine might produce toxic symptoms.
Jokinen
Mika J
MJ
Department of Anaesthesia and Intensive Care, Helsinki University Central Hospital, P.O. Box 340, 00029 HUS, Finland. Mika.Jokinen@hus.fi
Olkkola
Klaus T
KT
Ahonen
Jouni
J
Neuvonen
Pertti J
PJ
D000328:Adult; D000577:Amides / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D000779:Anesthetics, Local / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000890:Anti-Infective Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002045:Bupivacaine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D002939:Ciprofloxacin / Q000494:pharmacology*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D000077212:Ropivacaine; D013237:Stereoisomerism
C475526:3-OH-ropivacaine; D000577:Amides; D000779:Anesthetics, Local; D000890:Anti-Infective Agents; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D002939:Ciprofloxacin; D000077212:Ropivacaine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C025149:2',6'-pipecoloxylidide; D002045:Bupivacaine