Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2004
Randomized Controlled Trial Clinical TrialCiprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism.
Tizanidine, a centrally acting skeletal muscle relaxant, is metabolized mainly by cytochrome P450 (CYP) 1A2 and has a low oral bioavailability. The fluoroquinolone antibiotic ciprofloxacin is only a moderately potent inhibitor of CYP1A2. Our objective was to study the extent and mechanism of a possible interaction of ciprofloxacin with tizanidine. ⋯ Ciprofloxacin greatly elevates plasma concentrations of tizanidine and dangerously potentiates its hypotensive and sedative effects, mainly by inhibiting its CYP1A2-mediated metabolism, at least when administered 1 hour before tizanidine. Tizanidine seems to be a useful probe drug for measuring presystemic metabolism by CYP1A2. Care should be exercised when tizanidine is used concomitantly with ciprofloxacin.