Evaluation of the absorption from some commercial sustained-release theophylline products

  • Robert A. Upton
  • Jean-Francois Thiercelin
  • Theodor W. Guentert
  • Lloyd Sansom
  • J. Robert Powell
  • Peter E. Coates
  • Sidney Riegelman


Absorption of theophylline from three commercial products labeled as sustained release was compared to the absorption from a standard uncoated tablet (Searle 200-mg aminophylline tablet) in a single-dose study. Aminodur tablets (Cooper) and Slophyllin Gyrocap capsules (Dooner) had bioavailability (100.2%±19.8% and 98.5%±13.8%) statistically indistinguishable from that of the standard but showed significantly slower absorption (peak times of 10,4±2.8 and 4.36±1.35 hr) and lower peak plasma concentrations (13.9±4.5 and 22.6±3.5gmg/ml/g dose) than the standard (tpeak,1.52±0.45 hr; Cpeak,28.l±6.2μg/ml/g dose). The time of the plasma concentration peak (2.47±1.38 hr) after a dose of Tedral S.A. (Warner/Chilcott) was not statistically different from that after the standard, but both the peak concentration (16.0±3.9 gmg/ml/g dose) and bioavailability (76.0±18.4%) were. Multiple-dose projections from single-dose data indicate that of the three test products only Aminodur maintains reasonably constant interdose plasma levels during 12 hourly dosing. With an 8 hourly dosing schedule Gyrocaps also might be satisfactory. Reasonable predictions of the plasma concentrations arising from Aminodur doses have been made using a single-compartment body model and assuming input from an outer followed by an inner layer of the tablet.

Typically a single dose of a preparation designed for constant release of drug over 12 hr should not produce a plasma concentration plateau in subjects with an average 6.1-hr drug half-life. The apparent plateau in the mean plasma profile (i.e., concentrations at each sampling time averaged over all subjects) for Aminodur doses is evaluated. The interpretation commonly being implied in the publication of mean profiles from bioavailability studies is misleading, particularly when applied to sustained-release preparations.

Key words

theophylline absorption bioavailability sustained release tablets plasma concentrations mean plasma concentrations steady-state projections 


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Copyright information

© Plenum Publishing Corporation 1980

Authors and Affiliations

  • Robert A. Upton
    • 1
  • Jean-Francois Thiercelin
    • 1
  • Theodor W. Guentert
    • 1
  • Lloyd Sansom
    • 1
  • J. Robert Powell
    • 1
  • Peter E. Coates
    • 1
  • Sidney Riegelman
    • 1
  1. 1.Department of PharmacyUniversity of CaliforniaSan Francisco

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