Summary
In new of previous contradictory results, the possible interaction between the loop diuretic furosemide and theophylline was re-evaluated in 12 healthy volunteers with a steady-state plasma theophylline level.
Two doses of furosemide 20 mg at a 4 h interval did not influence the steady-state plasma concentration of theophylline despite causing a moderate diuresis. Urinary recovery of theophylline and its metabolites amounted to 106±21% of the dose without furosemide and 96±19% of the dose with furosemide, demonstrating that there was no influence on the enteral absorption of theophylline of the furosemide treatment. After the first dose of furosemide the fractional renal clearance (CLR1) of theophylline (fractional = hourly sampling period) changed in parallel with the urinary flow rate, without a significant difference between treatment with and without furosemide. After the second dose of furosemide, CLR1 was increased in the first hour and then it declined to levels far lower than the control value.
This unexpected result could explain the unchanged plasma concentration of theophylline during furosemide treatment.
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References
Bartoli E, Arras S, Faedda R, Soggia G, Satta A, Olmea NA (1980) Blunting of furosemide diuresis by aspirin in man. J Clin Pharmacol 20: 452–458
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41
Conlon PF, Grambau GR, Johnson CE, Weg JG (1981) Effect of intravenous furosemide on serum theophylline concentration. Am J Hosp Pharm 38: 1345–1347
D'Arcy PF (1983) Drug interactions with new drugs. Pharm Int 4: 285–291
Grambau GR, Conlon PF, Johnson CE, Weg JG (1978) Predicted versus actual plasma theophylline concentrations at steady-state and as influenced by furosemide. Am Rev Respir Dis 177: 66
Gundert-Remy U, Hildebrandt R (1983) Binding of theophyline and its metabolites to human plasma proteins. Br J Clin Pharmacol 16: 573–574
Gundert-Remy U, Hildebrandt R (1984) Linear metabolism but nonlinear kinetics of theophylline. Naunyn Schmiedebergs Arch Pharmacol 325 [Suppl R87]: 345
Hammarlund MM, Paalzow LK, Odlind B (1984) Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis. Eur J Clin Pharmacol 26: 197–207
Jacobs MH, Senior RM, Kessler G (1976) Clinical experience with theophylline. J Am Med Assoc 235: 1983–1986
Jonkman JHG (1984) Biopharmaceutical and pharmacokinetic drug interactions with theophylline. In: Jonkman JHG (eds) The use of sustained release theophylline in the treatment of chronic reversible airway obstruction. Excerpta Medica, Amsterdam, pp 98–110
Jonkman JHG, Upton RA (1984) Pharmacokinetic drug intractions with theophylline. Clin Pharmacokinet 9: 309–334
Levy G, Koysooko R (1976) Renal clearance of theophylline in man. J Clin Pharmacol 16: 329–332
McElnay JC, Smith GD, Helling DK (1982) A practical guide to interactions involving theophylline kinetics. Drug Intell Clin Pharm 16: 533–542
Nakagawa RS, Conlon PF, Johnson CE (1982) Theophylline — furosemide interaction? Am J Hosp Pharm 39: 242
Sachs L (1978) Angewandte Statistik. Springer, Berlin Heidelberg New York, pp 244–246
Shinn AF, Shrewsbury RP (1985) Evaluations of drug interactions. Mosby, St. Louis Toronto Princeton, pp 631–660
Tang-Liu DD, Tour TN, Riegelmann S (1982) Urine flow-dependence of theophylline renal clearance in man. J Pharmacokinet Biopharm 10: 351–364
Tobak JW, Gilman ME (1983) Theophylline — furosemide inactivation? Pediatrics 71: 140–141
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Jänicke, U.A., Krüdewagen, B., Schulz, A. et al. Absence of a clinically significant interaction between theophylline and furosemide. Eur J Clin Pharmacol 33, 487–491 (1987). https://doi.org/10.1007/BF00544241
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DOI: https://doi.org/10.1007/BF00544241