Bayesian derived predictions for twice daily theophylline under outpatient conditions and an assessment of optimal sampling times.

Abstract

1. The accuracy of a computerised method of pharmacokinetic interpretation of a single serum theophylline concentration, employing the statistical technique of Bayesian analysis, has been evaluated for an oral slow release form of theophylline using twice daily dosing. 2. Twenty-four hour steady state serum theophylline concentration-time profiles of one Uniphyllin Continus 400 mg tablet (Napp Laboratories) every 12 h were measured in 15 patients. These profiles demonstrated a diurnal variation of theophylline absorption which was faster during the day. 3. Revised predictions of the profiles were generated by Bayesian analysis using a single serum theophylline concentration taken during a previous outpatient appointment. Comparing the predicted and measured profiles, the accuracy of the Bayesian method is considered more than adequate for clinical purposes. 4. The predictions produced by the revised estimates were statistically less biased and more precise than those derived by a theophylline algorithm using population data. 5. The mean prediction errors of the revised estimates of the day and night-peak drug concentrations were -0.55 mg l-1 and -0.21 mg l-1 whilst those of the evening and morning troughs were 1.17 mg l-1 and 0.41 mg l-1, respectively. 6. Analysis of the predictive and relative performance of the samples drawn during the profile revealed that the sample taken prior to a morning dose produced the most accurate predictions. 7. There was no statistical difference in the relative predictive performance of samples drawn up to 4 h before or 2 h after the morning dose. It is, therefore, recommended that all serum theophylline concentrations to be used in Bayesian analysis, should be drawn within this period.