Biomedical subjects

H Chrystyn

Publications and source records attributed to H Chrystyn.

62 records · Page 4Linked to original sources

PubMed1991

An assessment of population-based and Bayesian methods to individualize digoxin doses shortly after the start of therapy for atrial fibrillation.

The accuracy of population-based methods and of Bayesian analysis to predict individual digoxin pharmacokinetic variables have been evaluated by their ability to predict a measured peak and trough serum digoxin concentration. We studied 13 digitalized patients (three women) whose mean (range) age and weight was 65.8 (60-78) years and 76.6 (68-101.6) kg and who had stable renal function. The population-based methods (using a clearance of 48.87 + 0.87 x creatinine clearance in ml/h/kg and volume of distribution, in litres, of either 7.3 x weight (kg) or 269 + 3.12 x creatinine clearance) were more than adequate for clinical purposes. The mean prediction errors of a measured steady-state peak concentration from these two population methods were -0.074 and 0.013 microgram/l respectively, whilst those of a measured trough concentration were -0.058 and 0.005 microgram/l. Bayesian analysis, using a sample drawn 11 h after the dose on day five of therapy, gave overall the least biased and most precise of the revised estimates. The mean prediction errors of peak and trough values using this sample were 0.069 and -0.005 microgram/l respectively. As expected, the closer the sample was drawn to the time of the trough concentration the more precise were the Bayesian-derived predictions. The value of the Bayesian technique to individualize digoxin doses could not be validated because it was not possible to distinguish between this and the population methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

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

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.

Administration, Oral↗

PubMed1988

Dose response relation to oral theophylline in severe chronic obstructive airways disease.

OBJECTIVE: To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline. DESIGN: Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data. This was followed by random assignment to four consecutive two month treatment periods--placebo and low, medium, and high dose, as assessed by serum concentrations of theophylline. Respiratory function and exercise performance was assessed at the end of each two month period. SETTING: Chest unit in district hospital. PATIENTS: Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited; 33 aged 53-73 years completed the study. INTERVENTIONS: Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted, when 400 mg was given. Targets for the steady state serum theophylline concentrations were 5-10 mg/l in the low dose period, 10-15 mg/l in the medium dose, and 15-20 mg/l in the high dose period. ENDPOINTS: Respiratory function as measured by forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate, slow vital capacity, and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived. Exercise performance assessed by six minute walking test and diary cards using visual analogue scale. MEASUREMENTS AND MAIN RESULTS: The forced expiratory volume in one second, forced vital capacity, and peak expiratory flow rate changed only slightly (about 13%) over the range of doses. There was a linear dose dependent fall of trapped gas volume from 1.84 l (SE 0.157) to 1.42 l (0.152), 1.05 l (0.128), and 0.67 l (0.102) during the placebo and low, medium, and high dose treatment periods. Mean walking distance increased by up to 55.6 m (20%). There was a modest improvement in dyspnoea as the dose of theophylline was increased. Side effects were mostly minor but they became more frequent as the dose was increased. CONCLUSION: The fall in trapped gas volume may reflect an improvement in peripheral ventilation (associated with treatment with theophylline) which is less apparent in the more common tests of lung function used in patients with chronic obstructive airways disease.

Administration, Oral↗

PubMed1988

The accuracy and stability of Bayesian theophylline predictions.

Pharmacokinetic parameters for theophylline were determined in 33 patients (3 women), mean age 61.2 years and weight 74.6 kg using the following three methods: (a) standard one-compartmental model calculations, assuming 100% bioavailability, after a single dose of theophylline syrup (mean dose 413 mg); (b) drug nomogram; and (c) Bayesian analysis. Patients entered a randomised study of three two-monthly dosage regimens using low, medium, and high theophylline twice daily doses. These doses produced mean (+/- SE) steady-state serum theophylline concentrations of 6.3 (+/- 0.4), 12.1 (+/- 0.3) and 18.3 (+/- 0.5) mg/L, respectively. A fourth period of placebo (2-month duration) was also included. At the end of each treatment period the measured serum theophylline concentration of each patient was compared with those predicted by each of the above three methods. The revised estimates derived from Bayesian analysis produced the least biased [mean prediction error (ME)] and most precise (mean squared prediction error) predictions for all three dosage periods. Statistical analysis of relative performance demonstrated that the difference in precision between the revised estimates and those of the other two methods was significant (p less than 0.05) with the magnitude of the difference increasing with dose. The revised estimates were also found to be less biased (p less than 0.05) than those of the nomogram. The ME (+/- SE) of the revised estimates for the low, medium, and high dosage periods was 0.34 (+/- 0.30), -0.02 (+/- 0.22) and -0.48 (+/- 0.31) mg/L, respectively.

Bayes Theorem↗

PubMed1988

Validation of the use of Bayesian analysis in the optimization of gentamicin therapy from the commencement of dosing.

A computer program based on the statistical technique of Bayesian analysis has been adapted to run on several microcomputers. The clinical application of this method for gentamicin has been validated in 13 patients with varying degrees of renal function by a comparison of the accuracy of this method to a predictive algorithm method and one using standard pharmacokinetic principles. Blood samples for serum gentamicin analysis were taken after the administration of an intravenous loading dose of gentamicin. The results produced by each method were used to predict the peak and trough values measured on day 3 of therapy. Of the three methods studied, Bayesian analysis, using a serum gentamicin concentration drawn four hours after the initial dose, was the least biased and the most precise method for predicting the observed levels. The mean prediction error of the Bayesian analysis method, using the four-hour sample, was -0.03 mg/L for the peak serum concentration and -0.07 mg/L for the trough level on day 3. Using this method the corresponding root mean squared prediction error was 0.60 mg/L and 0.36 mg/L for the peak and trough levels, respectively.

Aged↗

PubMed1987

The accuracy of a pharmacokinetic theophylline predictor using once daily dosing.

1. The accuracy of a computer based pharmacokinetic prediction method based on Bayesian analysis has been evaluated for an oral show release form of theophylline. 2. In 83 patients from seven centres 24 h serum theophylline concentration-time profiles were measured under a variety of circumstances. 3. Revised predictions of 24 h serum theophylline concentration profiles were generated by Bayesian analysis using single serum drug concentrations taken before, during and after the study days in different subgroups of those patients. Comparing the predicted and measured profiles the mean prediction error (bias) was 0.05 mg l-1 for peak concentrations and 0.04 mg l-1 for trough concentrations during once daily dosing. The corresponding root mean squared prediction errors (precision) were 2.59 and 1.17 mg l-1, respectively. 4. This accuracy is considered more than adequate for clinical purposes. 5. The technique can be used with a variety of other drugs and can form a valuable part of a routine therapeutic drug monitoring service.

Adult↗

PubMed1986

A comparison of graphical nomogram methods with a computerized Bayesian analysis method in the interpretation of serum phenytoin concentrations.

A study was performed to compare the predictability of a reported Bayesian graphical method, the drug nomogram used in the Bayesian Computer Method and the Driessen Nomogram with that of a computerized Bayesian analysis method in the interpretation of serum phenytoin concentrations. It was found that the results generated by the graphical method were similar to those of the computer with a mean prediction error of 3.9 mg/day in the dose to achieve a concentration at steady-state of 20 ml/l. Overall the results of the graphical method were less biased and had more precision with a significant improvement in relative precision (P less than 0.01) than the initial estimate or Driessen methods.

Adolescent↗

PubMed1985

Dosage of tobramycin in cystic fibrosis--a short report.

A 15 kg, 7-year-old girl with cystic fibrosis was admitted with a chest infection. It was found that a tobramycin, 12 mg/kg/day (standard recommended dose 6-7.5 mg/kg/day), was required to obtain acceptable plasma levels and that the volume of distribution varied in line with the patient's weight changes.

Child↗