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.

U2 - 10.1111/j.1365-2125.1984.tb04990.x

DO - 10.1111/j.1365-2125.1984.tb04990.x

M3 - Article

C2 - 6691882

SN - 0306-5251

VL - 17

SP - 1

EP - 8

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 1

ER -