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

Abstract

We compared a least squares regression method, used prospectively to individualise the intravenous aminophylline and oral theophylline dosage of 48 patients, with 3 other pharmacokinetic methods - Chiou's, the steady-state clearance and the Bayesian - used retrospectively to analyse the same patient data. Methods were compared on the basis of the similarity of their parameter estimates and the accuracy with which serum concentrations during subsequent intravenous and oral therapy could be forecast, assuming each method's parameter estimates. The least squares and Bayesian programs were able to fit data from all but 4 and 2 patients, respectively. Mean absolute prediction errors were of the order of 20% for serum concentrations during intravenous therapy, and of the order of 40% for serum concentrations during oral therapy. The accuracy of the least squares, Bayesian and steady-state clearance methods were similar, but the accuracy of Chiou's method was comparable only when the 2 serum concentrations needed for the method were measured between 11 and 17 hours apart; an interval which corresponds to the 1.0 to 1.5 half-lives previously suggested as desirable for implementation of the Chiou method.

Development of a Therapeutic Drug Monitoring Strategy for the Optimization of Vincristine Treatment in Pediatric Oncology Populations in Africa

“…Since its introduction, the Bayesian estimation of pharmacokinetic parameters and its use in pharmacokinetic-guided dosing have been well established. It has been described for numerous drugs including vancomycin, 31,32 mycophenolic acid, 33 theophylline, 34,35 aminoglycoside antibiotics, [36][37][38] antiepileptic drugs, [38][39][40] digoxin, 41 and chemotherapeutics such as paclitaxel 42 and carboplatin. 43 However, for vincristine exposure, Bayesian estimation is not suitable under current clinical constraints.…”

An Updated Comparison of Drug Dosing Methods

“…Hurley et al (1988) compared a least squares regression method (FUNFIT, Veng-Pedersen 1977), used prospectively to individualise oral and intravenous theophylline dosage in 48 patients, with the pharmacokinetic method of Chiou et al (1978), the steady-state clearance method of Slotfeldt et al (1979), and a Bayesian method (Abbott Pharmacokinetic Systems) for their ability to predict clearance and subsequent theophylline concentrations retrospectively. Hurley et al (1988) compared a least squares regression method (FUNFIT, Veng-Pedersen 1977), used prospectively to individualise oral and intravenous theophylline dosage in 48 patients, with the pharmacokinetic method of Chiou et al (1978), the steady-state clearance method of Slotfeldt et al (1979), and a Bayesian method (Abbott Pharmacokinetic Systems) for their ability to predict clearance and subsequent theophylline concentrations retrospectively.…”

Pharmacokinetic Optimisation of Asthma Treatment

“…(1988 or the Bayesian method (Sheiner et al 1979) can be used. Comparison of the accuracy of these methods has been discussed extensively elsewhere (Erdman et al 1991;Hurley & MacNeil 1988;Reiter et al 1992). The investigators all agree that these methods provide useful estimates of individual pharmacokinetic parameters, but do not replace the need to measure serum theophylline concentrations at steady-state.…”