Prediction of optimum oral theophylline dose in patients with obstructive airways disease.

Abstract

1 The hypothesis that a logarithmic correlation exists between the plasma theophylline concentrations 6 h after a test dose C(6) and the maintenance dose calculated to achieve a desired drug concentration during chronic oral administration (DM,CALC) was tested. A nomogram based on this relationship was evaluated as a means of predicting the optimum dose of theophylline in 14 patients with obstructive airways disease (DM,PMRD).2 Each patient was given 5 mg/kg theophylline intravenously (i.v.) and plasma theophylline concentrations were measured for 12 h thereafter including one exactly 6 h after commencing the i.v. infusion C(6). Pharmacokinetic parameters derived from the plasma concentration-time curve were used to establish DM,CALC for a concentration of 10 ,ug/ml. DM,PPED was obtained from the nomogram using both the optimum and the actual values for C(6). Subsequently oral sustained-release theophylline was administered and the dose adjusted to establish a trough concentration of approximately 10 ,ug/ml. This dose was then corrected arithmetically, assuming a linear relationship between dose and plasma level, to represent that required to achieve a plasma concentration of exactly 10 ,ug/ml (DM,AC-)- 3 The correlation between C(6) and log DM,CALC was confirmed (r = 0.97 P < 0.001), validating the hypothesis. DM,ACT was found to correlate significantly with DM,PRED (r = 0.90, P < 0.01) substantiating the value of the nomogram. In nine of the 14 patients, DM,ACr corresponded satisfactorily to DM,PRED. In the remaining five, for whom DM,ACT lay outside the 95% confidence limits for the predicted dose, DM,PRED in general underestimated DMACT, an advantage in a drug with a low therapeutic index. The predictive error for DM,PRED was lower than that for DM,CALC and the bias using either method was not significant. 4 The results suggest that a single plasma theophylline assay following a test dose, and the nomogram may be useful in simplifying optimal theophylline administration.

Prediction of maintenance oral theophylline dosage using single oral doses in patients with obstructive airways disease.

“…We have previously shown that the predictive errors contained in this nomogram, although considerable, are similar to those en- x-squared = 1.7: NS 10 0 1 countered using more detailed pharmacokinetic data (Taylor et al, 1983). In his original hypothesis, Koup pointed out that typical errors in the magnitude of the test dose, sampling time, and assay technique, ought not to affect the nomogram dose predictions in any substantial way (Koup et al, 1979).…”

A Comparison of the Accuracy of a Least Squares Regression, a Bayesian, Chiou??s and the Steady-State Clearance Method of Individualising Theophylline Dosage

“…Estimated and 'actual' pharmacokinetic parameters (Anderson et al 1981), or predicted and observed serum concentrations (Coleman & Hedberg 1983), or predicted and 'actual' dosage requirements (Taylor et al 1983) have been used to assess pharmacokinetic methods. Correlation coefficients and linear regression techniques have then been used to compare predicted and observed variables (Anderson et al 1981;Taylor et al 1983), although Sheiner and Beal (1981) have clearly demonstrated the folly of using such methods to assess predictive accuracy.…”

Theophylline dose prediction.

“…The within run and between Q n t <. t -, X t vs run coefficients of variation for the assay were 2-5% -Z 7 (mean = 15-0 mg/l; n = 10) and 5 (2) Where Cl is the total body clearance of theophylline and the product of k, and Vd, and T is the dose …”