Teofilin Konsantrasyon Verisi ile Solunum Sistemi Hastalığı Olan Hastaların Farmakokinetik Modellemesi Üzerine Bir Not

Abstract

Pharmacokinetics which describes the time course of drug absorption, distribution, metabolism, and excretion in the body is critical in formulating drug therapy. Nonlinear Mixed Effects (NLME) models are popularly used in many longitudinal studies, including human immunodeficiency viral dynamics, pharmacokinetic analyses, and studies of growth and decay.This work aimed to develop efficient NLME models for analyzing Theophylline concentration data within the pharmacokinetics framework. The data consisted of Theophylline concentration (mg/L) measurements of 12 asthmatic patients who were treated with oral Theophylline. The serum concentrations were measured at 11 times per subject over 25 hours periods. Hence, a total of 132 observations were obtained. Six different pharmacokinetics models were fitted in a step-wise manner to these data within the framework of NLME techniques. The best of these models that yielded the most efficient estimates of the physiological factors such as absorption rate (<i>k_α</i>), elimination rate (<i>k_e</i>), and clearance (<i>C_l</i>) in the patients was determined using suitable model selection criteria. The results showed that the clearance and absorption rate have mixed effects with estimated values of <i>C_l</i> = 0.0397 and <i>k_α</i> = 1.54203 (for fixed effects) while the effect of the elimination rate in all the patients is fixed with the estimated value of <i>k_e</i> =0.0860. Also, the low estimated standard deviations of the random effects components of <i>C_l</i> (0.1699) and <i>k_α</i>(0.6384)over the entire samples is a clear evidence that the fitted model was quite consistent and efficient.Results from this study would further serve as useful guides to clinicians and drug developers in the proper formulation and administration of Theophylline therapy on patients suffering from respiratory diseases.