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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Haley TJ. Metabolism and pharmacokinetics of theophylline in human neonates, children and adults. Drug Metab Rev 1983;14:295–335.
Hendeles L, Massanari M, Weinberg M. Theophylline. In: Evans WE, Schentag JJ, Jusko WJ, eds. Applied pharmacokinetcs. Spokane: Applied Therapeutics Inc., 1986:1105–88.
Jonkman JHG, Upton RA. Pharmacokinetic drug interactions with theophylline. Clin Pharmacokinet 1984;9:309–44.
Thomson RD, Nagasawa HT, Jenne JW. Determination of theophylline and its metabolites in human urine and serum by high-pressure liquid chromatography. J Lab Clin Med 1974;85:584–93.
Yesair DW, Branfman AR, Callahan MM. Human disposition and some biochemical aspects of methylxanthines. In: Spiller GA, ed. The methylxanthine beverages and foods: chemistry, consumption and health aspects. New York: Alan R. Liss Inc., 1984:215–33.
Wijnands WJA, Van Herwaarden CLA, Vree TB. Enoxacin raises plasma theophylline concentrations. Lancet 1984;2:108–9.
Wijnands WJA, Vree TB, Van Herwaarden CLA: Enoxacin decreases the clearance of theophylline in man. Br J Clin Pharmacol 1985;20:583–8.
Wijnands WJA, Vree TB, Van Herwaarden CLA. The influence of quinolone derivates on theophylline clearance. Br J Clin Pharmacol 1986;22:677–83.
Davies BI, Maesen FPV, Teengs JP. Serum and sputum concentrations of enoxacin after single oral dosing in a clinical and bacteriological study. J Antimicrob Chemother 1984;14(suppl C):83–9.
Raoof S, Wollschlager C, Khan F. Serum theophylline levels are increased by ciprofloxacin (Bay 9867), a new quinolone antibiotic. Chest 1985;88:32.
Wijnands WJA, Van Griethuysen AJA, Vree TB, Van Klingeren B, Van Herwaarden CLA. Enoxacin in lower respiratory tract infections. J Antimicrob Chemother 1986;18:719–27.
Logamann C, Ohnhaus EE. Enoxacin, a differential inhibitor of the microsomal liver enzyme system in man. Abstract 26th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, USA, 1987.
Okazaki O, Miyazaki K, Tachizawa H. Lack of effect of ofloxacin on theophylline pharmacokinetics in rats. Chemotherapy 1987;502.
Tang-Liu DDS, Williams RL, Riegelman S. Nonlinear theophylline elimination. Clin Pharmacol Ther 1982; 31:358–69.
Grygiel JJ, Wing LMH, Farkas J, Birkett DJ. Effects of allopurinol on the theophylline metabolism and clearance. Clin PHarmacol Ther 1979;26:660–7.
Miners JO, Attwood J, Birkett DJ. Theobromine metabolism in man. Drug Metab Dispos 1982;10:672–5.
Betlach CJ, Tozer TN. Biodisposition of theophylline. Effect of aromatic hydrocarbon treatment in mice. Drug Metab Dispos 1980;8:271–3.
Levy G, Koysooko R. Renal clearance of theophylline in man. J Clin Pharmacol 1976;16:329–32.
Tang-Liu DDS, Williams RL, Riegelman S. Disposition of caffeine and its metabolites in man. J Pharmacol Exp Ther 1983;24:180–5.
Grygiel JJ, Birkett DJ. Cigarette smoking and theophylline clearance and metabolism. Clin Pharmacol Ther 1981;30:491–6.
Rosenberry KR, Defusco CJ, Mansmann HC, McGeady SJ. Reduced theophylline half-life induced by carbamazepine therapy. J Pediatr 1983;702:472–4.
Manfredi RL, Vesell ES. Inhibition of theophylline metabolism by long term allopurinol administration. Clin Pharmacol Ther 1981;29:224–9.
Campbell MA, Plachetka JR, Jackson JE, Moon JF, Finley PR. Cimetidine decreases theophylline clearance. Ann Intern Med 1981;95:68–9.
Grygiel JJ, Miners JO, Drew R, Brikett DJ. Differential effects of cimetidine on theophylline metabolic pathways. Eur J Pharmacol 1984;26:335–40.
Jackson JE, Powell JR, Wandell M. Cimetidine decreases theophylline clearance. Am Rev Respir Dis 1981;123:615–7.
Reitberg DP, Berhard H, Schentag JJ. Alteration of theophylline clearance and half-life by cimetidine in normal volunteers. Ann Intern Med 1981;95:582–5.
Renton KW, Gray JD, Hung OR, Depression of theophylline elimation by erythromycin. Clin Pharmacol Ther 1981;30:422–6.
Roberts RK, Grice J, McGuffie C, Heilbronn L. Oral contraceptive steroids impair the elimination of theophylline. J Lab Clin Med 1983;101:821–5.
Tornatore KM, Kanarkowski R, McCarthy TL, Gardner MJ, Jusko WJ. Effect of chronic oral contraceptive steroids on theophylline disposition. Eur J Clin Pharmacol 1982;23:129–34.
Wijnands WJA, Vree TB, Baars AM, Van Herwaarden CLA. Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin, and pefloxacin during maintenance treatment with theophylline. Drugs 1987;34(suppl 1):159–69.
Nazario M. The hepatic and renal mechanisms of drug interactions with cimetidine. Drug Intell Clin Pharm 1986;20:342–8.
About this article
Cite this article
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
- Drug interactions