The influence of ofloxacin and enoxacin on the metabolic pathways of theophylline in healthy volunteers

A pilot study

Abstract

The pharmacokinetic parameters of theophylline and its major metabolites were measured in two healthy volunteers, after the administration of theophylline alone and during co-medication with ofloxacin, 200 mg twice daily, or enoxacin, 200 mg twice daily. During enoxacin co-medication, elimination half-lives of theophylline increased from 8.7 h to 17.4 h and from 6.1 h to 12.3 h, respectively. As the renal clearance of theophylline did not change, the decreased elimination of theophylline during enoxacin co-medication must result from a reduced metabolic clearance. Enoxacin co-medication caused a clearly decreased formation of the metabolitesI-methyluric acid and 3-methylxanthine, formed by N-demethylation, whereas the C-8 oxidation of theophylline was less influenced compared to the blank. Enoxacin's interference with the theophylline disposition is predominantly based on the inhibition of the microsomal N-demethylation. Ofloxacin co-medication did not induce a change in the plasma parameters or renal excretion of theophylline and its metabolites.

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Correspondence to T. B. Vree.

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Wijnands, W.J.A., Janssen, T.J., Guelen, P.J.M. et al. The influence of ofloxacin and enoxacin on the metabolic pathways of theophylline in healthy volunteers. Pharmaceutisch Weekblad Scientific Edition 10, 272–276 (1988). https://doi.org/10.1007/BF02219667

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Keywords

  • Drug interactions
  • Enoxacin
  • Metabolism
  • Ofloxacin
  • Pharmacokinetics
  • Theophylline