Abstract
1 Binding of theophylline (80 mumol/l) was determined in serum from healthy subjects by equilibrium dialysis and by ultrafiltration, using [3H]-theophylline, at 22 degrees C and at different pH-values. pH was regulated by gassing with CO2 or by dialysing the serum against a phosphate buffer before use. 2 Binding of theophylline in serum was 34-38% determined by equilibrium dialysis and 41-45% determined by ultrafiltration at pH 7.4-7.5. The protein concentration in serum decreased by 12-16% during equilibrium dialysis and increased by 20% during ultrafiltration. The intersubject variation in binding was small. 3 Binding of theophylline in serum was pH-dependent with 25-30% bound at pH 7.0 and 58-60% bound at pH 8.1-8.3. Binding was significantly correlated to the fraction of ionized theophylline. 4 The binding of theophylline in normal human serum is about 35-40% at pH 7.4 and 22 degrees C. The difference in binding observed between equilibrium dialysis and ultrafiltration may be explained by the opposite changes in protein concentration during the experiment. 5 Control of pH is necessary to obtain physiologically relevant data on drug binding in serum.
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- Aslaksen A., Bakke O. M., Vigander T. Comparative pharmacokinetics of theophylline and aminophylline in man. Br J Clin Pharmacol. 1981 Mar;11(3):269–273. doi: 10.1111/j.1365-2125.1981.tb00533.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleetham J. A., Ginsburg J. C., Nakatsu K., Wigle R. D., Munt P. W. Resin hemoperfusion as treatment for theophylline-induced seizures. Chest. 1979 Jun;75(6):741–742. doi: 10.1378/chest.75.6.741. [DOI] [PubMed] [Google Scholar]
- Hendeles L., Weinberger M., Johnson G. Monitoring serum theophylline levels. Clin Pharmacokinet. 1978 Jul-Aug;3(4):294–312. doi: 10.2165/00003088-197803040-00003. [DOI] [PubMed] [Google Scholar]
- Jacobs M. H., Senior R. M., Kessler G. Clinical experience with theophylline. Relarionships between dosage, serum concentration, and toxicity. JAMA. 1976 May 3;235(18):1983–1986. doi: 10.1001/jama.235.18.1983. [DOI] [PubMed] [Google Scholar]
- Koysooko R., Ellis E. F., Levy G. Relationship between theophylline concentration in plasma and saliva of man. Clin Pharmacol Ther. 1974 May;15(5):454–460. doi: 10.1002/cpt1974155454. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lesko L. J., Tabor K. J., Johnson B. F. Theophylline serum protein binding in obstructive airways disease. Clin Pharmacol Ther. 1981 Jun;29(6):776–781. doi: 10.1038/clpt.1981.110. [DOI] [PubMed] [Google Scholar]
- Mangione A., Imhoff T. E., Lee R. V., Shum L. Y., Jusko W. J. Pharmacokinetics of theophylline in hepatic disease. Chest. 1978 May;73(5):616–622. doi: 10.1378/chest.73.5.616. [DOI] [PubMed] [Google Scholar]
- Piafsky K. M., Sitar D. S., Rangno R. E., Ogilvie R. I. Theophylline disposition in patients with hepatic cirrhosis. N Engl J Med. 1977 Jun 30;296(26):1495–1497. doi: 10.1056/NEJM197706302962603. [DOI] [PubMed] [Google Scholar]
- Simons K. J., Simons F. E., Briggs C. J., Lo L. Theophylline protein binding in humans. J Pharm Sci. 1979 Feb;68(2):252–253. doi: 10.1002/jps.2600680238. [DOI] [PubMed] [Google Scholar]
- Wilting J., van der Giesen W. F., Janssen L. H., Weideman M. M., Otagiri M., Perrin J. H. The effect of albumin conformation on the binding of warfarin to human serum albumin. The dependence of the binding of warfarin to human serum albumin on the hydrogen, calcium, and chloride ion concentrations as studied by circular dichroism, fluorescence, and equilibrium dialysis. J Biol Chem. 1980 Apr 10;255(7):3032–3037. [PubMed] [Google Scholar]
- Zwillich C. W., Sutton F. D., Neff T. A., Cohn W. M., Matthay R. A., Weinberger M. M. Theophylline-induced seizures in adults. Correlation with serum concentrations. Ann Intern Med. 1975 Jun;82(6):784–787. doi: 10.7326/0003-4819-82-6-784. [DOI] [PubMed] [Google Scholar]