Individualization of theophylline infusion rate on the basis of a nonlinear compartmental pharmacokinetic model

Abstract

In the present paper, a nonlinear compartmental model for theophylline pharmacokinetics is developed. The analytical solution of the model, in parametric form, is derived under plateau conditions for plasma metabolite concentration. The parameters are obtained from plasma and urine data using best fitting techniques and their values are used in order to calculate maintenance intravenous infusion. Numerical simulation is then performed in order to compare the drug concentration obtained by our approach with that of alternative intravenous regimens. The differences argue for individualized dosage regimens, since theophylline is a drug with a narrow therapeutic window and its concentration at the active sites strongly depends on characteristic parameters of the patient's response. Our results show that it is possible to estimate the patients' parameters during the first 8 h after intravenous administration of the drug and these parameters can be used to design an individualized dosage regimen in patients receiving theophylline intravenously.

Molecularly Imprinted Solid Phase Extraction Micro-column with Differential Pulsed Elution for Theophylline Determination

“…Interaction with theophylline was reported for two new oral macrolides, while some fluoroquinolones could inhibit the cytochrome P-450 enzyme system thereby causing increased serum concentrations of drugs like theophylline and caffeine (2). Since theophylline is a drug with a narrow therapeutic window (from 10 to 20 g/ml in serum) between therapeutic efficacy and adverse effects (3), and its concentration at the active sites strongly depends on characteristic parameters of the patient's response during the first 8 h after intravenous administration of the drug, it has recently been argued for an individualization of dosage regimen in patients (particularly neonates, children, aged, or critically ill) receiving theophylline intravenously (4,5).…”