Recent studies in laboratory rodents have revealed that circadian oscillation in the physiologic functions affecting drug disposition underlies the dosing time-dependent change in pharmacokinetics. However, it is difficult to predict the circadian change in the drug pharmacokinetics in a diurnal human by using the data collected from nocturnal rodents. In this study, we used cynomolgus monkeys,...

Physiological changes in pregnancy, including changes in body composition and metabolic enzyme activity, can alter drug pharmacokinetics. A semi-mechanistic metabolism model was developed to describe the pharmacokinetics of two cytochrome P450 3A (CYP3A) substrates, midazolam and nifedipine, in obstetrics patients. The model parameters were optimized to fit the data of oral midazolam pharmacoki...

Few studies investigating the population pharmacokinetics of linezolid in critically ill patients have been reported, yielding controversial results. Therefore, a population pharmacokinetic analysis using NONMEM was performed to thoroughly understand the pharmacokinetics of unbound linezolid in plasma. Data were obtained from 10 healthy volunteers and 24 septic patients. Intensive sampling was ...

Changes of mycophenolic acid (MPA) pharmacokinetics with aging were investigated in rats. We also compared the effect of concomitant amoxicillin/clavulanate combination (CVA/AMPC) on the pharmacokinetics of MPA in 4-week-old and 12-week-old rats (the package insert of CVA/AMPC warns of possible interaction with MPA). Four-week-old rats showed a 1.4-fold higher total body clearance of MPA and a ...

Tatiana Tatarinova, Laboratory of Applied Pharmacokinetics, University of Southern California, Los Angeles, USA, [email protected] Alyona Chubatiuk Department of Mathematics, University of Southern California, Los Angeles, California, USA, [email protected] Michael Neely Laboratory of Applied Pharmacokinetics, University of Southern California, Los Angeles, USA, [email protected] Alan Sc...