Pharmaceutisch Weekblad

, Volume 7, Issue 1, pp 10–14 | Cite as

Food and a sustained release theophylline tablet on chronic dosing: bioavailability, peak-trough and trough-trough differences

  • M. Lagas
  • J. H. G. Jonkman
Original Articles


The bioavailability of theophylline and the serum concentration fluctuations after administration of a sustained release tablet (Theograd® 250 mg, one tablet twice daily) were studied in the steady state in six volunteers. On postprandial administration of the 250 mg tablets the bioavailability was 89±16%. Good sustained release properties were obtained provided that the tablets were taken after a meal; Cmax was 7.9±2.0 mg.l−1,tmax was 5.3±1.6 h, the peak-trough difference was 2.3±0.6 mg.l−1 and the serum concentration fluctuation was accounted for 42.8±11.2%. It was shown that on postprandial administration the mean serum concentration-time profile could be successfully calculated by means of multiple dose projection from single dose data. However, when the a.m. dose was given on an empty stomach and the p.m. dose 3 h after a meal, it appeared not to be possible to use the single diurnal dose data for calculation of the steady state serum concentration-time profile: the experimentally observed a.m. trough levels were significantly higher than the p.m. trough values and also the observed mean serum concentration was significantly higher than the calculated level. The possible causes for this discrepancy are extensively discussed.


Theophylline Sustained Release Trough Level Empty Stomach Release Property 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Lagas M, Jonkman JHG. Greatly enhanced bioavailability of theophylline on postprandial administration of a sustained release tablet. Eur J Clin Pharmacol 1983;24:761–7.Google Scholar
  2. 2.
    Lagas M, Jonkman JHG. Influence of food on the rate and extent of absorption of theophylline after single dose oral administration of a sustained release tablet. Int J Clin Pharmacol Ther Toxicol, in press.Google Scholar
  3. 3.
    Jonkman JHG, Schoenmaker R, Greving JE, De Zeeuw RA. Rapid selective theophylline serum and saliva assay by means of high pressure liquid chromatography. Pharm Weekbl [Sci] 1980;2:49–53.Google Scholar
  4. 4.
    Hendeles L, Iafrate RP, Weinberger M. A clinical and pharmacokinetic basis for the selection and use of slow release theophylline products. Clin Pharmacokinet 1984;9:95–135.Google Scholar
  5. 5.
    Upton RA, Thiercelin JF, Guentert TW, et al. Evaluation of the absorption from some commercial sustained-release theophylline products. J Pharmacokinet Biopharm 1980;8:131–49.Google Scholar
  6. 6.
    Jenne JW, Wyze E, Rood FS, McDonald FM. Pharmacokinetics of theophylline. Application to adjustment of the clinical dose of aminophylline. Clin Pharmacol Ther 1972:13:349–60.Google Scholar
  7. 7.
    Mitenko PA, Ogilvie RI. Rational intravenous doses of theophylline. N Eng J Med 1973;289:600–3.Google Scholar
  8. 8.
    Weinberger MM, Hendeles L. Experience with theophylline for the management of chronic asthma. Eur J Resp Dis 1980;(suppl):109.Google Scholar
  9. 9.
    Svedmyr K. Effects of oral theophylline combined with oral and inhaled beta2-adrenostimulants in asthmatics. Allergy 1982;37:119–27.Google Scholar
  10. 10.
    Sprangler DL, Kalof DD, Bloom FL, Wittig HJ. Theophylline bio-availability following oral administration of six sustained-release preparations. Ann Allergy 1978;40:6–12.Google Scholar
  11. 11.
    Dasta J, Mirtallo JM, Altman M. Comparison of standard- and sustained-release theophylline tablets in patients with chronic obstructive pulmonary disease. Am J Hosp Pharm 1979;36:613–7.Google Scholar
  12. 12.
    Ritschel WA. Handbook of basic pharmacokinetics. 2nd ed. Hamilton: Drug Intelligence, 1980.Google Scholar
  13. 13.
    Kelly HW, Murphy S. Efficacy of a 12-hours sustained-release preparation in maintaining therapeutic serum theophylline levels in asthmatic children. Pediatrics 1980;66:97–102.Google Scholar
  14. 14.
    Isles AF, Scott PH, Tabachnik E, et al. Circadian variation in theophylline disposition in asthmatic children. In: Soyka LF, Redmond GP, red. Drug metabolism in the Immature Human. New York: Raven Press: 241–7.Google Scholar
  15. 15.
    Scott PH, Tabachnik E, MacLeod S, Correia J, Newth C, Levison H. Sustained-release theophylline for childhood asthma: evidence for circadian variation of theophylline pharmacokinetics. J Pediatr 1981:99:476–9.Google Scholar
  16. 16.
    Newth CJL, Isles AF. Comparison at steady state of sustained-release theophylline tablet and capsules. J Asthma 1982;19:145–9.Google Scholar
  17. 17.
    Taylor DR, Duffin D, Kinney CD, MacDevitt DG. Investigation of diurnal changes in the disposition of theophylline. Br J Clin Pharmacol 1983;:16:413–6.Google Scholar
  18. 18.
    Jonkman JHG, Van der Boon WJV, Balant LP, Schoenmaker R, Holtkamp A. Chronopharmacokinetics of theophylline after sustained and intravenous administration to adults. Eur J Clin Pharmacol 1984;26:215–22.Google Scholar
  19. 19.
    Giacona N, Elvin AT, Seligsohn R, et al. Diurnal variation in theophylline elimination. Drug Intell Clin Pharm 1983;17:452.Google Scholar
  20. 20.
    Nakano S, Watanabe H, Naqai K, Sasayama H, Ogawa N. Time-of-day effect on theophylline kinetics following oral dosing with aminophylline. IRCS Medical Services 1982;10:798–9.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1985

Authors and Affiliations

  • M. Lagas
    • 1
  • J. H. G. Jonkman
    • 2
  1. 1.Laboratory for Pharmaceutical ResearchSL RodenThe Netherlands
  2. 2.Laboratory for Drug Analysis (Drug Monitoring Unit)AC AssenThe Netherlands

Personalised recommendations