Evaluation of a novel Bayesian method for individualizing theophylline dosage. 1988

U Stein, and M Oellerich, and G W Sybrecht, and B Schneider
Institut für Klinische Chemie, Medizinische Hochschule Hannover, Federal Republic of Germany.

A novel Bayesian drug dosing program (Abbott Pharmacokinetic Systems, Theophylline Program) was evaluated. The predictive accuracy of this method was assessed in 10 healthy volunteers receiving single intravenous test doses. Estimates for clearance and distribution volume were compared with those obtained from the area under the curve. The observed prediction error depended largely on sampling time. The deviations were lowest for the distribution volume during the first 60 min and for clearance at 12 hours after theophylline administration. Furthermore the Bayesian technique was prospectively evaluated in 10 hospitalized and 22 outpatients treated with sustained-release theophylline preparations (Uniphyllin, Bronchoretard, PulmiDur). Predictive precision and accuracy were adequate, if theophylline was given twice daily. The highest predictive accuracy was achieved in outpatients, if predictions were based on trough concentrations. In 19/22 outpatients prediction errors were within a clinically acceptable range (mean prediction error +/- standard deviation; -0.6 +/- 2.1 mg/l). Moreover in hospitalized patients (n = 5) with twice-daily maintenance regimens, concentration-time curves could mainly be predicted with sufficient accuracy. Hospitalized patients (n = 5) with once-daily dosing showed large fluctuations between peak and trough theophylline concentrations in serum. In these patients a reliable prediction of the concentration-time curves was not possible apparently due to non-linearity of theophylline kinetics. Relatively large prediction errors were found in one patient with acute viral respiratory illness and 3 patients with altered absorption. Despite certain limitations the clinical application of the Bayesian forecasting method tested appears to be promising.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D001499 Bayes Theorem A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result. Bayesian Analysis,Bayesian Estimation,Bayesian Forecast,Bayesian Method,Bayesian Prediction,Analysis, Bayesian,Bayesian Approach,Approach, Bayesian,Approachs, Bayesian,Bayesian Approachs,Estimation, Bayesian,Forecast, Bayesian,Method, Bayesian,Prediction, Bayesian,Theorem, Bayes
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D013806 Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP. 1,3-Dimethylxanthine,3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione,Accurbron,Aerobin,Aerolate,Afonilum Retard,Aquaphyllin,Armophylline,Bronchoparat,Bronkodyl,Constant-T,Elixophyllin,Euphylong,Glycine Theophyllinate,Lodrane,Monospan,Nuelin,Nuelin S.A.,Quibron T-SR,Slo-Phyllin,Somophyllin-T,Sustaire,Synophylate,Theo Von Ct,Theo-24,Theo-Dur,Theobid,Theocin,Theoconfin Continuous,Theodur,Theolair,Theolix,Theon,Theonite,Theopek,Theophylline Anhydrous,Theophylline Sodium Glycinate,Theospan,Theostat,Theovent,Uniphyl,Uniphyllin,Uniphylline,1,3 Dimethylxanthine,Anhydrous, Theophylline,Constant T,ConstantT,Ct, Theo Von,Glycinate, Theophylline Sodium,Quibron T SR,Quibron TSR,Slo Phyllin,SloPhyllin,Sodium Glycinate, Theophylline,Somophyllin T,SomophyllinT,Theo 24,Theo Dur,Theo24,Theophyllinate, Glycine,Von Ct, Theo

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