Metabolism of caffeine in type 1 diabetic patients by physiologically based pharmacokinetics modeling

Abstract

Background: Disease related physiological changes can cause alterations in the metabolism and disposition of drugs. Diabetes is a chronic condition and can cause numerous alterations in the physiological functions in patients which may cause alterations in drug metabolism. However often clinical trials fail to include diabetic patients in early drug development. Methods: Physiologically based pharmacokinetic modelling (PBPK) concepts can be utilized to predict the pharmacokinetics of drugs based on the available data on physiological characteristics of patients. Using PBPK concepts alterations in metabolism of caffeine in type 2 diabetic patients in comparison to healthy counterparts was reported earlier, in this study we extended to predict the alterations in metabolism and disposition of caffeine in type 1 diabetic patients. Results and conclusions: This study outcome predicts that the oral clearance of caffeine is about 60% and the AUC 0-24 of caffeine is 40% less in type 1 diabetic patients in comparison to healthy volunteers. This study generates a caution towards possible alterations in disposition of caffeine and for drugs which are substrate of CYP1A2 enzymes and have similar physio-chemical properties as caffeine. Further confirmatory clinical evidence is warranted to ascertain the research outcome of this study.