Prediction of response to theophylline in chronic bronchitis

B. Whiting, A. W. Kelman, A. D. Struthers

    Research output: Contribution to journalArticle

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    Abstract

    In chronic bronchitis, intersubject variability in both theophylline pharmacokinetics and pharmacodynamics must be taken into account if the drug is to be used to its best advantage. Both kinds of variability can be integrated into a model which relates the steady state concentration of theophylline to simultaneously measured ventilatory response (most conveniently, the FVC). In a group of 56 patients with chronic bronchitis, the mean +/- s.d. linear response to increasing steady state concentrations of theophylline was 0.04 +/- 0.012 1 microgram-1 ml, starting from a mean +/- s.d. pretreatment FVC of 1.58 +/- 0.791. Using these population parameter values, with or without a pretreatment FVC and/or one steady state concentration -FVC observation, it was possible to predict the degree of response which would be achieved by a smaller group of 20 similar patients. These estimates were obtained using a mathematical procedure based on Bayesian Probability Theory and Maximum Likelihood Estimation. Estimates of the overall response in individual patients allowed prediction of the response at any steady state concentration. These estimates were unbiased and accurate enough for clinical use when they were based on a pretreatment FVC and/or one paired steady state concentration -FVC observation.
    Original languageEnglish
    Pages (from-to)1-8
    Number of pages8
    JournalBritish Journal of Clinical Pharmacology
    Volume17
    Issue number1
    DOIs
    Publication statusPublished - 1984

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    Chronic Bronchitis
    Theophylline
    Probability Theory
    Observation
    Pharmacokinetics
    Pharmaceutical Preparations
    Population

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    title = "Prediction of response to theophylline in chronic bronchitis",
    abstract = "In chronic bronchitis, intersubject variability in both theophylline pharmacokinetics and pharmacodynamics must be taken into account if the drug is to be used to its best advantage. Both kinds of variability can be integrated into a model which relates the steady state concentration of theophylline to simultaneously measured ventilatory response (most conveniently, the FVC). In a group of 56 patients with chronic bronchitis, the mean +/- s.d. linear response to increasing steady state concentrations of theophylline was 0.04 +/- 0.012 1 microgram-1 ml, starting from a mean +/- s.d. pretreatment FVC of 1.58 +/- 0.791. Using these population parameter values, with or without a pretreatment FVC and/or one steady state concentration -FVC observation, it was possible to predict the degree of response which would be achieved by a smaller group of 20 similar patients. These estimates were obtained using a mathematical procedure based on Bayesian Probability Theory and Maximum Likelihood Estimation. Estimates of the overall response in individual patients allowed prediction of the response at any steady state concentration. These estimates were unbiased and accurate enough for clinical use when they were based on a pretreatment FVC and/or one paired steady state concentration -FVC observation.",
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    Prediction of response to theophylline in chronic bronchitis. / Whiting, B.; Kelman, A. W.; Struthers, A. D.

    In: British Journal of Clinical Pharmacology, Vol. 17, No. 1, 1984, p. 1-8.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Prediction of response to theophylline in chronic bronchitis

    AU - Whiting, B.

    AU - Kelman, A. W.

    AU - Struthers, A. D.

    PY - 1984

    Y1 - 1984

    N2 - In chronic bronchitis, intersubject variability in both theophylline pharmacokinetics and pharmacodynamics must be taken into account if the drug is to be used to its best advantage. Both kinds of variability can be integrated into a model which relates the steady state concentration of theophylline to simultaneously measured ventilatory response (most conveniently, the FVC). In a group of 56 patients with chronic bronchitis, the mean +/- s.d. linear response to increasing steady state concentrations of theophylline was 0.04 +/- 0.012 1 microgram-1 ml, starting from a mean +/- s.d. pretreatment FVC of 1.58 +/- 0.791. Using these population parameter values, with or without a pretreatment FVC and/or one steady state concentration -FVC observation, it was possible to predict the degree of response which would be achieved by a smaller group of 20 similar patients. These estimates were obtained using a mathematical procedure based on Bayesian Probability Theory and Maximum Likelihood Estimation. Estimates of the overall response in individual patients allowed prediction of the response at any steady state concentration. These estimates were unbiased and accurate enough for clinical use when they were based on a pretreatment FVC and/or one paired steady state concentration -FVC observation.

    AB - In chronic bronchitis, intersubject variability in both theophylline pharmacokinetics and pharmacodynamics must be taken into account if the drug is to be used to its best advantage. Both kinds of variability can be integrated into a model which relates the steady state concentration of theophylline to simultaneously measured ventilatory response (most conveniently, the FVC). In a group of 56 patients with chronic bronchitis, the mean +/- s.d. linear response to increasing steady state concentrations of theophylline was 0.04 +/- 0.012 1 microgram-1 ml, starting from a mean +/- s.d. pretreatment FVC of 1.58 +/- 0.791. Using these population parameter values, with or without a pretreatment FVC and/or one steady state concentration -FVC observation, it was possible to predict the degree of response which would be achieved by a smaller group of 20 similar patients. These estimates were obtained using a mathematical procedure based on Bayesian Probability Theory and Maximum Likelihood Estimation. Estimates of the overall response in individual patients allowed prediction of the response at any steady state concentration. These estimates were unbiased and accurate enough for clinical use when they were based on a pretreatment FVC and/or one paired steady state concentration -FVC observation.

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