Prediction of response to theophylline in chronic bronchitis.

Whiting, B.; Kelman, Andrew W.; Struthers, AD

doi:10.1111/j.1365-2125.1984.tb04990.x

Cited by 24 publications

(3 citation statements)

References 11 publications

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“…The Bayesian method can be applied in clinical practice by using a number of computer programs [8][9][10][11][12]. Among these, the ADVISE program [12], designed for the Hewlett-Packard HP-85/87 microcomputer, is one of the most commonly used.…”

Section: Introductionmentioning

confidence: 99%

A calculator program for clinical application of the Bayesian method of predicting plasma drug levels

Ruffo

Messori

Grasela

et al. 1985

Computer Programs in Biomedicine

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A pharmacokinetic program that allows individualization of drug dosage regimens through the Bayesian method is described. The program, which is designed for the Hewlett-Packard HP-41 CV calculator, is based upon the one-compartment open model with either instantaneous or zero-order absorption. Individualized estimation of the patient's kinetic parameters (clearance and volume of distribution) is performed by analyzing the plasma levels measured in the patient as well as considering the population data of the drug. After estimating the individual kinetic parameters by the Bayesian method, the program predicts the dosage regimen that will elicit the desired peak and trough plasma levels at steady state. For comparison purposes, the least-squares estimates for clearance and volume of distribution are calculated, and dosage prediction can also be made on the basis of the least-squares estimates. The least-squares estimates can be used to calculate population pharmacokinetic parameters according to the Standard Two-Stage method. Several examples of clinical use of the program are presented. The examples refer to patients with classic hemophilia who were treated with Factor VIII concentrates. In these patients, the Bayesian kinetic parameters of Factor VIII have been estimated through the calculator program. The Bayesian parameter estimates generated by the HP-41 have been compared with those determined by a Bayesian program (ADVISE) designed for microcomputers.

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Section: Introductionmentioning

confidence: 99%

A calculator program for clinical application of the Bayesian method of predicting plasma drug levels

Ruffo

Messori

Grasela

et al. 1985

Computer Programs in Biomedicine

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“…The difficulty in obtaining a serum theophylline level >10 µg·mL -1 in the long-term treatment of reversible airway obstruction is well-known, because of the difficulties in using this drug [14]. However, the therapeutic benefit of theophylline in treating airways obstruction is dose-related, and can be observed at levels as low as 5 µg·mL -1 , particularly when theophylline is given in conjunction with β 2 -agonists [15,16]. In our study, only nine subjects in the theophylline group showed a serum theophylline concentration <5 µg·mL -1 at the end of the active treatment, suggesting that compliance with the treatment was acceptable.…”

Section: Discussionmentioning

confidence: 99%

Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. European Study Group

Paggiaro¹,

Giannini²,

Franco³

et al. 1996

Eur Respir J

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The median percentage of nights with no asthma symptoms rose from 14% in both groups at baseline to 71% with salmeterol and to 46% with theophylline (p=0.044). There was also a significant increase for salmeterol in the median percentage of nights with no rescue salbutamol use (from 36 to 86%) compared with theophylline (from 71 to 78%; p=0.002). The mean morning PEF increased from 337 L·min -1 in the salmeterol group and 332 L·min -1 in the theophylline group to 372 and 357 L·min -1 , respectively. No significant difference between the two treatments was observed for PEF, symptoms or additional salbutamol medication during the day. The incidence of gastrointestinal symptoms (gastric irritation, nausea and vomiting) was greater among patients receiving theophylline (11%) than with salmeterol (3%).These findings suggest that inhaled salmeterol is more effective in relieving symptoms of asthma, and better tolerated than theophylline in patients with moderateto-severe asthma. Eur Respir J., 1996Respir J., , 9, 1689Respir J., -1695 The clinical efficacy of salmeterol, the first of a new class of long-acting β 2 -agonists, has been demonstrated in comparison with other short-acting β 2 -agonists, such as salbutamol and terbutaline [1,2]. As oral theophylline is an asthma drug widely used in many countries, especially in Europe, this study was planned to compare the effects of salmeterol with oral slow-release theophylline. The new slow-release preparations of oral theophylline allow quite stable levels of serum theophylline concentration with one or two daily administrations, and they are commonly accepted for treatment of chronic reversible airway obstruction [3]. In this respect, the comparison between oral slow-release theophylline and salmeterol, both drugs with a long-lasting (up to 12 h) bronchodilation achieved by twice daily administration, seems of particular interest for long-term treatment of reversible airway obstruction. In a previous study, the effect of salmeterol was compared with theophylline over 2 weeks in a double-blind, cross-over study [4], showing that salmeterol produced a better effect on asthma symptoms and peak expiratory flow (PEF) values than theophylline in subjects with moderate asthma. Salmeterol was also shown to be more effective than a combination of slow-release theophylline and ketotifen in producing disappearance of nocturnal symptoms, lung function and rescue salbutamol use, during a 2 week period of treatment in 115 patients with nocturnal asthma [5].This large multicentre study was conducted in 24 European Centres, in order to compare the efficacy and tolerability of salmeterol with oral theophylline in the treatment of moderate-to-severe asthma. Subjects and methods SubjectsTwo hundred and forty three patients with moderateto-severe asthma were recruited into the study. Inclusion criteria were: 1) male or female aged 18-70 yrs; 2) symptoms of asthma (dyspnoea, wheeze, cough) for at least 1 year; 3) reversible airway obstruction (forced expiratory volume in one second (FEV1)...

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“…This is due to the fact that in some studies no parameters for a concentration-effect relationship are given, [30] while others have used a linear concentration-effect modeU 31,32] It can therefore only tentatively be concluded that the EC so for bronchodilation is 10 to 15 mg/L.…”

Section: Theophyllinementioning

confidence: 97%

Pharmacokinetic-Pharmacodynamic Modelling As Applied to Bronchial Asthma

Koopmans

Jonkers

Braat

et al. 1995

Clinical Pharmacokinetics

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Quantitative aspects of drug action in humans are traditionally studied using dose-response curves. Information obtainable from such studies includes the minimum effective dose and the maximum tolerated dose; these experiments give some information on the desired dose and dosage interval, and on interindividual variation. They are very time consuming (because multiple doses must be given without a carry-over effect), and thus are not very efficient. Moreover, a prediction of the drug effect is usually only possible for the maximum effect, as such studies do not give detailed information on the time-course of drug action after a single dose.Recent years have seen a movement away from the traditional approach towards so-called pharmacokinetic-pharmacodynamic studies (PK-PD studies). The latter methodology has the advantages that only a single dose is needed, that a more-orless complete concentration-effect relationship is obtained, and that a possible time delay between drug in plasma and drug effect can be incorporated into the PK-PD model. It is even possible to incorporate aspects of drug action, such as, for example, the development of tolerance. The drug effect can therefore be predicted at any time after administration, in a way quite like the prediction of drug concentrations with a pharmacokinetic model.

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Prediction of response to theophylline in chronic bronchitis.

Cited by 24 publications

References 11 publications

A calculator program for clinical application of the Bayesian method of predicting plasma drug levels

A calculator program for clinical application of the Bayesian method of predicting plasma drug levels

Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. European Study Group

Pharmacokinetic-Pharmacodynamic Modelling As Applied to Bronchial Asthma

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