The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects.

Abstract

1 The mechanism of the interaction between ciprofloxacin and theophylline was investigated in nine healthy subjects. 2 Subjects were given a single oral dose of theophylline (3.4 mg kg-), before and after 60 h of ciprofloxacin therapy at a dose of 500 mg twice daily. 3 Ciprofloxacin reduced the oral clearance of theophylline by 19% (-7.73 ± 6.42 ml kg-' h-' (95% confidence limits -12.66, -2.79)). Some subjects (group A, n = 4) showed little decrease in clearance (mean 4.4%; -1.6 ± 0.7 ml kg-' h-1 (-2.6, -0.5)), whereas others (group B, n = 5) showed a marked decrease (mean 30%; -12.7 ± 3.7 ml kg-' h-1 (-17.2, -8.1)).4 Comparing groups A and B, the decrease in oral clearance of theophylline in group B could not be ascribed to differences in the AUC of ciprofloxacin. Group A subjects showed only slight inhibition of 1-demethylation (-12.8 ± 5.5% (-21.5, -4.0)), while group B subjects showed a significantly greater inhibition of 1-demethylation (-49.9 ± 9.8% (-62.1, -37.7)), 3-demethylation (-44.8 ± 8.6% (-55.4, -34.1)) and 8-hydroxylation (-27.0 ± 3.7% (-31.6, -22.4)). 5 The results suggest that inter-individual variability in the inhibition of theophylline metabolism by ciprofloxacin can be attributed to inter-individual differences in the level of CYP1A2 expression and/or in the degree of inhibition of hepatic CYP1A2 and CYP3A4. 6 The interaction between ciprofloxacin and theophylline can be clinically significant. However, uniform decrease in the theophylline dose is not warranted because there is a negligible change in theophylline clearance when ciprofloxacin is coadministered in a substantial proportion of patients.

Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2?mediated presystemic metabolism

“…Ciprofloxacin, at a usual dose of 500 mg twice daily, had a strong pharmacokinetic interaction with tizanidine. However, this interaction differed qualitatively and quantitatively from the recently described fluvoxamine‐tizanidine interaction 6 and quantitatively from the previously published interactions of ciprofloxacin with other drugs 9 , 10 , 11 , 12 , 13 . Ciprofloxacin increased the AUC(0‐∞) of tizanidine by 10‐fold, in some subjects by up to 24‐fold, and the C max by 7‐fold, but in contrast to the effect of fluvoxamine, the elimination half‐life of tizanidine was prolonged only marginally.…”

“…However, this interaction differed qualitatively and quantitatively from the recently described fluvoxamine-tizanidine interaction 6 and quantitatively from the previously published interactions of ciprofloxacin with other drugs. [9][10][11][12][13] Ciprofloxacin increased the AUC(0-ϱ) of tizanidine by 10-fold, in some subjects by up to 24-fold, and the C max by 7-fold, but in contrast to the effect of fluvoxamine, the elimination half-life of tizanidine was prolonged only marginally. In previous reports, ciprofloxacin has only moderately (less than 2-fold) increased the AUC of other drugs that are metabolized by CYP1A2, including theophylline, 9,10 caffeine, 11 clozapine, 12 and ropivacaine.…”

In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19 and CYP2D6

“…Of note, TCL accumulates in rat liver [16] and if this can be extrapolated to humans, there may be subsets of patients (e.g. cigarette smokers), who are particularly vulnerable to TCL drug interactions, as is the case with the ciprofloxacin–theophylline interaction [42].…”

Farmakokinetyczne interakcje międzylekowe w oddziale intensywnej terapii – obserwacje jednoośrodkowe i przegląd piśmiennictwa

“…The effect of ciprofloxacin on the concentration of theophylline is much better documented and more significant; i.e. ciprofloxacin increases the concentration of theophylline by 17 to 113% [61,62]. The mechanism of this interaction involves strong inhibition of CYP1A2 metabolising theophylline [53].…”